Research Models

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254 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (240)
3xTg-AD, The LaFerla mouse B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax C7BL/6;129X1/SvJ;129S1/Sv APP, PSEN1, MAPT APP KM670/671NL (Swedish), MAPT P301L, PSEN1 M146V Single-cell embryos from mice with knock-in of PSEN1 with the PS1M146V mutation were injected with two human transgenes (APP with the Swedish mutation and MAPT with the P30IL mutation). Transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter. APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. The Jackson Lab; available through the JAX MMRRC Stock# 034830; Live Oddo et al., 2003 Yes
5XFAD, APP/PS1, Tg6799, Tg-5xFAD B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax C57BL/6 x SJL APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles. Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype. The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live. Research with this model is available from QPS Austria. Oakley et al., 2006 Yes
5XFAD, APP/PS1, Tg6799, Tg-5xFAD B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax C57BL6 APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer V. Age-dependent memory deficits, motor phenotype, and reduced anxiety. Available from The Jackson Laboratory, JAX MMRRC Stock# 034848 Jawhar et al., 2012, Richard et al., 2015 Yes
C57BL/6J APP APP KM670/671NL (Swedish), APP T714I (Austrian) Transgene-expressing mutant APP with the Swedish mutation (K670N/M671L) and the Austrian mutation (T714I) under the control of the Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months. Unknown. Optogenetic stimulation induced epileptic seizures. Unknown Yamada et al., 2009 Yes
GFP-(GA)50 C57BL/6J An adeno-associated viral (AAV) vector encoding 50 glycine-alanine (GA) repeats tagged with green fluorescent protein was injected into the ventricles of neonatal mice. Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Poly(GA)- and ubiquitin-positive inclusions in neurons are primarily cytoplasmic and also co-localize with HR23A and HR23B proteins and the nuclear pore complex proteins RanGAP1 and Pom121. Neuron loss and astrogliosis in cortex and hippocampus. Motor deficits, impaired coordination, hyperactivity, increased anxiety, and deficits in contextual and cued fear conditioning. Viral construct available through Leonard Petrucelli. Zhang et al., 2016 Yes
GFP–(GR)100 C57BL/6J An adeno-associated viral (AAV) vector encoding 100 glycine-arginine (GR) repeats tagged with green fluorescent protein was injected into the ventricles of neonatal mice. Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Progressive neuron loss in cortex and hippocampus, gliosis. Lacks poly(GR) inclusions. Rare TDP-43 inclusions. Progressive motor deficits and age-dependent cognitive impairment. Viral construct available through Leonard Petrucelli. Zhang et al., 2018 Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Abca7em#2Adiuj Trem2em1Adiuj/J C57BL/6J Abca7, APOE, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the rs3752246 SNP mutation (p.A1527G) into the Abca7 gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available January, 2019 from The Jackson Laboratory, Stock# 030283 The Jackson Laboratory Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Abca7em#1Adiuj Trem2em1Adiuj/J C57BL/6J Abca7, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-out mutation of the Abca7 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available January, 2019 from The Jackson Laboratory, Stock# 030320 The Jackson Laboratory Yes
Dan-amyloid, BRI2-Danish, ADan precursor protein Tg(Prnp-ITM2B*)6Jckr and Tg(Prnp-ITM2B*)7Jckr C57BL/6J ITM2B (BRI2) BRI2: Familial Danish Dementia (FDD) duplication Transgenic mice with human BRI2 gene containing the Familial Danish Dementia (FDD) mutation under the control of the Syrian hamster prion protein promoter. The FDD mutation is a 10-nucleotide duplication in the region of the stop codon in the BRI2 gene, resulting in a C-terminally elongated protein. ITM2B (BRI2): Transgenic Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present. Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype. Adult mice fail to gain weight with age. Alopecia. Kyphosis. Available through Mathias Jucker Coomaraswamy et al., 2010 Yes
5xFAD BxD (B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax x BXD[strain number] C57BL/6J X BXD[strain number] APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V “AD-BXD” refers to a panel of transgenic mouse strains, created by crossing 5XFAD mice to members of the BXD genetic reference panel. 5XFAD mice carry APP (with the Swedish, Florida, and London mutations) and PSEN1 (with M146L and L286V mutations) transgenes. The BXD genetic reference panel is a set of recombinant inbred mouse strains derived from crossing the C57BL/6J and DBA/2J inbred strains. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent. Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent. Individual AD-BXD strains are available as F1 hybrids from The Jackson Laboratory (each strain has its own stock number). Neuner et al., 2019 Yes
Amyloid β (A4) precursor-like protein 2 knock-out, APLP2 KO B6.129S7-Aplp2tm1Dbo/J 129S7,C57BL/6J; backcrossed to C57BL/6J Aplp2 Inactivation of the mouse APLP2 gene by deleting a 1.1kb region containing the promoter and exon 1 using a targeting vector containing a PGK-neomycin expression cassette for positive selection and a MC1-TK cassette for negative selection. Aplp2: Knock-Out Alzheimer's Disease Not observed. Not observed. Homozygous animals are viable, normal in size, fertile, and do not display any gross physical or behavioral abnormalities up to 22 months of age. No impairments in axonal outgrowth of olfactory neurons following bulbectomy. The Jackson Lab: Stock# 004142; Cryopreserved von Koch et al., 1997 No
APOE2 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE2 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. 2-fold higher level of steady state APOE in brain and higher APOE in serum compared with APOE3 and APOE4 KI animals. Highest levels of serum cholesterol and triglycerides after a 6hr fast. No longer available through Bruce Lamb Mann et al., 2004 No
E2F C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε2 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
APOE2 KI, APOE*2 KI B6.Cg-Apoeem3(APOE*)Adiuj/J C57BL/6J APOE APOE2 KI mice were generated by using CRISPR/Cas9 to introduce two point mutations (leading to arginine to cysteine substitutions at amino acids 130 and 176) in an existing humanized APOE4 knock-in allele (The Jackson Laboratory Stock# 027894). APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available for Registering Interest, The Jackson Laboratory, Stock# 029017 The Jackson Laboratory Yes
APOE2 Humanized Knock-in B6.129P2-Apoetm1(APOE*2)Mae N9 C57BL/6 APOE Targeted gene replacement of the endogenous murine APOE gene with the human APOE2 allele. Targeting construct included exons 2-4 of APOE2. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Characteristics of type III hyperlipoproteinemia. Plasma cholesterol and triglyceride levels 2-3x higher than APOE3 mice. Impaired clearance of very-low-density lipoprotein (VLDL) particles. Atherosclerotic plaques. Taconic: Stock# 1547-F and 1547-M Sullivan et al., 1998 Yes
E3F C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε3 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
APOE3 KI, APOE*3 KI B6(SJL)-ApoEem2(APOE*)Adiuj/J B6SJL APOE CRISPR/Cas9 used to introduce a point mutation (leading to an arginine-to-cysteine substitution at amino acid 130) into an existing humanized APOE4 knock-in allele. APOE: Knock-In Alzheimer's Disease No data. No data. The Jackson Laboratory, Stock # 029018; Live The Jackson Laboratory Yes
APOE3 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE3 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. Intermediate brain APOE and serum cholesterol levels compared with mice with knock-in of APOE4 or APOE2. No longer available through Bruce Lamb Mann et al., 2004 Yes
APOE3 Humanized Knock-in B6.129P2-Apoetm2(APOE*3)Mae N8 129 x C57BL/6; back-crossed to C57BL/6 APOE Targeted replacement of the endogenous mouse APOE gene with the human APOE3 allele. Targeting vector contained exons 2-4 of human APOE3. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. On a standard diet, homozygous mice have normal cholesterol and triglyceride levels, but are more susceptible than wild-type animals to diet-induced atherosclerosis. Taconic: Stock# 1548-F and 1548-M Sullivan et al., 1997 Yes
E4F C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε4 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
APOE4 KI, APOE*4 KI B6(SJL)-ApoEtm1.1(APOE*4)Adiuj/J B6SJL APOE Mouse ApoE exons 2, 3, and most of exon 4 replaced with human APOE sequence including exons 2, 3, 4 and a portion of the 3' UTR sequence. APOE: Knock-In Alzheimer's Disease No data. No data. The Jackson Laboratory, Stock # 027894; Live The Jackson Laboratory Yes
APOE4 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE4 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. Human ApoE is detectable in serum and astrocytes. Compared to mice with knock-in of APOE2 or APOE3, APOE4 mice had the lowest serum cholesterol after a 6 hour fast. No longer available through Bruce Lamb Mann et al., 2004 No
APOE4 Humanized Knock-in B6.129P2-Apoetm3(APOE*4)Mae N8 129 x C57BL/6, back-crossed to C57BL/6 APOE Targeted replacement of the endogenous murine APOE gene with the human APOE4 allele; targeting construct contained exons 2–4 of APOE4. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Increased risk of atherosclerosis. Elevated cholesterol, APOE, and APOB-48 on a high fat diet. Taconic: Stock# 1549-F or 1549-M Knouff et al., 1999 No
APOE KO, APOE -/-, APOE TM1 B6.129P2-Apoetm1Unc N11 129 x C57BL/6, back-crossed to C57BL/6 APOE Inactivation of the endogenous mouse APOE by homologous recombination and insertion of a neomycin cassette. APOE: Knock-Out Alzheimer's Disease Unknown. Unknown. Viable; healthy. Undetectable ApoE protein in plasma. Plasma cholesterol 5x higher than wild-type. Artherosclerotic lesions which progress to occlusions of coronary artery by 8 months. Taconic: Stock# APOE-M and APOE-F Piedrahita et al., 1992 No
B6-Tg/Thy1APP23Sdz B6.Cg-Tg(Thy1-APP)3Somm/J C57BL/6 APP APP KM670/671NL (Swedish) Transgene containing human APP (isoform 751) containing the Swedish (KM670/671NL) mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages. Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages. Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months. Available through The Jackson Laboratory Stock# 030504, Live Sturchler-Pierrat et al., 1997 Yes
B6.Cg-Tg(Thy1-APP)3Somm/J; Psen1tm1.1Tcs C57BL/6J APP, PSEN1 PSEN1 R278I This is a cross between APP23 mice, which overexpress APP751 with the Swedish mutation driven by the murine Thy1 promoter, and PSEN1 knock-in mice expressing human PSEN1 with the R278I mutation under the endogenous promoter. APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques. Short-term memory deficits apparent by 3-4 months as measured by the Y maze. Reduced γ-secretase activity. Available through Takaomi Saido Saito et al., 2011 Yes
APP(SL)PS1KI, APPxPS1-Ki, APPSL/PS1KI, APP(SL)/PS1(KI), APP/PS1KI The PS1KI line was established in 129SV and backcrossed >7 times to C57BL/6 background. The PS1KI were bred with APPSL mice on a C57BL background (two rounds) to obtain a homozygote PS1KI and heterozygote APP. APP, PSEN1 APP KM670/671NL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P This animal is a cross between a PSEN1 knock-in line and an APP over-expressing line. The PS1 knock-in line was generated by introducing two point mutations in the wild-type mouse PSEN1, corresponding to the mutations M233T and L235P. APP751SL overexpresses human APP751 carrying the London (V717I) and Swedish (K670N/M671L) mutations under the control of the Thy1 promoter. APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons. Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates. Viable and fertile. 6 month-old animals develop decreases in body weight, and a spinal deformity (kyphosis) is common. Impaired neurogenesis. Available through Thomas Bayer or Benoit Delatour Casas et al., 2004 Yes
tg13592 C57BL/6 x DBA/2 APP Transgene consisting of the signal plus 99-amino acid carboxyl-terminal sequence (SbC) of APP under the control of a cytomegalovirus enhancer/β-actin promoter. APP: Transgenic Alzheimer's Disease No neuropathology up to age 29 months; however, pathology reminiscent of inclusion body myopathy observed at 6-12 months: Aβ-immunoreactive deposits in skeletal muscle fibers. Muscle fibers with Aβ-immunoreactive deposits increased with age and also became vacuolated. Hypoactivity. The acquisition of place learning in the Morris water maze task was impaired. Higher cytochrome oxidase activity in thalamic nuclei. High levels of Aβ peptides in the plasma. Available through Ken-ichiro Fukuchi, University of Illinois College of Medicine at Peoria Fukuchi et al., 1996 No
APP-Dutch, Tg-APP(Dutch), APP E693Q, APP Dutch C57BL/6J-Tg(Thy1-APPDutch)#Jckr C57BL/6J APP APP E693Q (Dutch) Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter. APP: Transgenic Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed.  Unknown. Available through Mathias Jucker Herzig et al., 2004 Yes
Osaka, APP(OSK)-Tg, APP Osaka mutation transgenic, APPOSK-Tg mice, APPOSK mice B6C3F1, back-crossed to C57Bl/6 APP APP E693del (Osaka) Transgenic expression of human APP695 with the Osaka mutation driven by the mouse prion promoter. APP: Transgenic Alzheimer's Disease Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus. Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP. Available through Hiroshi Mori and Takami Tomiyama Tomiyama et al., 2010 Yes
APP KI, line ADF Apptm1Sud/J Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; C57BL/6 and maintained on a mixed background APP APP KM670/671NL (Swedish), APP V717I (London), APP E693Q (Dutch) Knock-in of wild-type mouse APP exon 16 (truncated after residue KM), FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene and an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations. APP: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Lab: Stock# 008390; Cryopreserved The Jackson Laboratory No
APP null, APP KO B6.129S7-Apptm1Dbo/J C57BL/6J APP Inactivation of the mouse APP gene by replacing a 3.8 kb sequence encoding the promoter and exon 1 with a neomycin resistance cassette. APP: Knock-Out Alzheimer's Disease Elevated reactive gliosis by 14 weeks in the hippocampus and parts of the neocortex. Impaired spatial learning as measured by the water maze at 4 and 10 months. Hypoactivity and decreased locomotor activity and forelimb grip strength. Homozygous knock-out mice weigh 15-20% less than age-matched wild-type mice. The Jackson Lab: Stock# 004133; Live Zheng et al., 1995 No
B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem2Adiuj Trem2em1Adiuj/J C57BL/6J APOE, App, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce a 94-bp deletion in exon 14 (APP695 numbering) of  the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (The Jackson Laboratory Stock# 028709). APOE: Knock-In; App: Knock-Out; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available February, 2019 from The Jackson Laboratory, Stock# 031722 The Jackson Laboratory Yes
APPNL-F/NL-F Apptm2.1Tcs/Apptm2.1Tcs C57BL/6 APP APP KM670/671NL (Swedish), APP I716F (Iberian) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations. APP: Knock-In Alzheimer's Disease Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. No overexpression of APP. Generates wild-type levels of AICD. Available through Takaomi Saido Saito et al., 2014 Yes
APPNL-G-F/NL-G-F, AppNL-G-F Apptm3.1Tcs/Apptm3.1Tcs C57BL/6 APP APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). APP: Knock-In Alzheimer's Disease Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 6 months as measured by the Y maze. No overexpression of APP. Wild-type levels of AICD. Available through Takaomi Saido Saito et al., 2014 Yes
AppNL-G-F/MAPT double knock-in, AppNL-G-F/MAPT dKI C57BL/6J App, MAPT APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) AppNL-G-F mice (mouse App sequence modified to contain a humanized Aβ region and the Swedish, Iberian, and Arctic mutations linked to AD) were crossed with MAPT knock-in mice (entire genomic sequence of murine Mapt, from exon 1 to exon 14, replaced with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region). App: Knock-In; MAPT: Knock-In Alzheimer's Disease Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F. Deficits in the Y-maze test of working memory, similar to AppNL-G-F. Compared with AppNL-G-F mice, AppNL-G-F/MAPT double knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain. Available through Takaomi Saido, RIKEN Center for Brain Science. Saito et al., 2019, Hashimoto et al., 2019 Yes
APPPS1-21 B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6J APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 L166P Human transgenes APP KM670/671NL and PSEN1 L166P, both under the control of the Thy1 promoter. Integration site is on lower arm of chromosome 2 between 40 and 60 cm. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.  Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. Aβ42 concentration in CSF decreases with age, with a 50% reduction by 6 months and an 80% reduction by 18 months. Aβ40 concentration also decreases, but less robustly (45% by 18 months). CSF concentration of total tau increases, starting at 6 months, and reaches a 5-fold increase by 18 months. Available through Mathias Jucker Radde et al., 2006 Yes
APPswe/PSEN1dE9/MAPT, APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221 B6.C3 x B6.129 x FVB APP, PSEN1, MAPT APP KM670/671NL (Swedish), PSEN1: deltaE9 APPswe/PSEN1dE9 mice were crossed with B6.129-Tg(CK-tTa) mice where the CaMKIIa promotor drives expression of tetracycline transactivator (tTA) in forebrain neurons. Offsping were then crossed to the Tg21221 line with a responder transgene of wildtype human tau. APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed. No data. N/A APPswe/PSEN1dE9 mice available through JAX MMRRC Stock# 034829. Jackson et al., 2016 Yes
Tg2576;Pdgfrβ+/- APPsw mice on C57BL/6; Pdgfrβ+/- mice on 129S1/SvlmJ. APP, PDGFRB APP KM670/671NL (Swedish) Progeny of APPsw transgenics (Tg2576) crossed with pericyte-deficient mice. Tg2576 express human APP with the Swedish double mutation driven by the hamster prion promoter. Pericyte-deficient mice were made by disrupting the Pdgfrβ gene using a PGKneobpA expression cassette to replace a 1.8 kb genomic segment spanning the signal peptide to the second immunoglobulin domain of PDGFRβ. APP: Transgenic; PDGFRB: Knock-Out Alzheimer's Disease Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus. Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition. Progressive loss of pericytes due to reduced Pdgfrβ signaling. Early and progressive blood brain barrier breakdown, indicated by cerebral accumulation of IgG. Reduced microvascular circulation, indicated by reduced capillary length. Available through Berislav Zlokovic Sagare et al., 2013 Yes
APPSwDI/NOS2 bigenic mice, APPSDI/NOS2KO, CVN B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6J; C57BL/6N APP, NOS2 APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) APPSwDI x NOS2 knockout animals. APPSwDI transgene expresses APP (isoform 770) with Swedish, Dutch, and Iowa mutations under the control of the mouse Thy1 promoter. NOS2 was disrupted by homologous recombination. The calmodulin binding domain of NOS2 was replaced by the neomycin resistance gene and the reading frame disrupted. APP: Transgenic; NOS2: Knock-Out Alzheimer's Disease Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. Decreased neuropeptide Y staining throughout the hippocampus, particularly in the CA3 region and subiculum. The Jackson Lab; available through the JAX MMRRC Stock# 034849; Cryopreserved. Charles River: CVN mouse Colton et al., 2008, Wilcock et al., 2008 Yes
APPSw, hAPPSwe (line 71) , hAPPSwe (line 72), huAPPSw B6.D2-Tg(Thy1-APPSwe)71Blt; B6.D2-Tg(Thy1-APPSwe)72Blt C57BL/6, DBA/2, crossed to C57BL/6 APP APP KM670/671NL (Swedish) Transgene with human APP751 with the Swedish mutation driven by the Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Amyloid plaques by 17-18 months in the neocortex and hippocampus with detection of 5-10 fold more Aβ40 than Aβ42. Plaque burden significantly lower than in the double transgenic PS2APP. Lower levels of insoluble Aβ40 and Aβ42 than the PS2APP mouse at 16-18 months. Unknown. Available through Laurence Ozmen Richards et al., 2003 No
R1.40, APPK670/M671, R1.40-YAC B6.129-Tg(APPSw)40Btla/Mmjax (129X1/SvJ x 129S1/Sv)F1-Kitl<+> APP APP KM670/671NL (Swedish) A 650 kb YAC transgene containing the entire human APP gene and ~250 kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J. APP: Transgenic Alzheimer's Disease By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months. Unknown. Increased mortality in young homozygous animals, especially females. At 3-4 months mice maintained on the C57BL/6J background exhibit spontaneous seizure-like activity as measured by EEG and are more susceptible to kainic acid-induced seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034831; Cryopreserved Lamb et al., 1997 Yes
APP(695)Swe C3B6-Tg(APP695)3Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP KM670/671NL (Swedish) Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain and the Swedish mutation under the control of the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age. Congenic animals showed normal reference and working memory up to 12-14 months. The Jackson Lab; available through the JAX MMRRC Stock# 034828; Cryopreserved Borchelt et al., 1996, Savonenko et al., 2003 Yes
B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP KM670/671NL (Swedish) Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain carrying the Swedish mutation under the control of the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Age-dependent increase in Aβ42, with low levels at 6-14 months and high levels at 24-26 months. No cognitive impairment in tasks of reference or working memory at 12-14 months. More than half of the female hemizygous mice do not survive past 15 months of age. The Jackson Lab; available through the JAX MMRRC Stock# 034835; Cryopreserved Savonenko et al., 2003, Borchelt et al., 1996 No
APP YAC Swe/Lon (line J1.96), B6-J1-96 B6.129S4-Tg(APPSwLon)96Btla/Mmjax 129S4/SvJae-derived J1 ES cells; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717I (London) A 650 kb YAC transgene containing the entire human APP gene carrying the Swedish and London mutations with ~ 250 kb of flanking sequence; founder animals (line J1.96) have a single copy of the transgene. APP: Transgenic Alzheimer's Disease No amyloid plaques observed at 2 years. Unknown. The Jackson Lab; available through the JAX MMRRC Stock# 034837; Cryopreserved Lamb et al., 1997 No
APPSwe (line C3-3)/PSEN1(A246E)(line N-5), APP/PS1, APPswe + PS1 (A246E), APP + PS1, AP mouse, C3-3/N-5 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/Mmjax Origin: (C57BL/6J x C3H/HeJ)F2 APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 A246E Double transgenic mice; cross of mice expressing human PSEN1 with the A246E mutation driven by the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation driven by the mouse prion promoter. Chimeric APP was created by replacing the mouse Aβ sequence with the cognate human sequence. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus. Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task. Increased irritability. The Jackson Lab: Stock# 003378; Cryopreserved Borchelt et al., 1997, Borchelt et al., 1996 Yes
APPSwe(line C3-3) X PS1dE9 (line S-9), C3-3/PS1-dE9, C3-3 x S-9 B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J Line C3-3: C57BL/6J; Line S-9: hybrid strain C3H/HeJ;C57BL/6J) backcrossed to C57BL/6J APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 Double transgenic mice: 1) Line C3-3: mice express a chimeric mouse/human APP gene (isoform 695) carrying the Swedish mutation and 2) Line S-9: mice express a mutant human PSEN1 gene carrying the deletion of exon 9 (dE9) driven by the mouse prion promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers. Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months. At 19 months, small but significant decrease in acetylcholinesterase activity in the hippocampus and choline acetyl transferase (ChAT) in the hippocampus and cortex. The Jackson Lab; available through the JAX MMRRC Stock# 034833; Cryopreserved Savonenko et al., 2005 Yes
APP/PS1, C57BL/6J APPswePsen1de9, B6.APBTg B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6J APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on the original hybrid C57BL/6 x C3H background were backcrossed with C57BL/6J mice. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina. Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age. A substantial proportion of APPswe/PSEN1dE9 mice exhibit electrographic and behavioral seizures. Available from the Jackson Laboratory, JAX MMRRC Stock# 034832 (formerly Jackson Lab Stock #005864) Minkeviciene et al., 2008, Minkeviciene et al., 2009 Yes
APP/PS1, APPswe/PS1deltaE9, line 85, APP(swe) + PSEN1DeltaE9, APdE9, Borchelt mice B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6;C3H APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 Co-injection of a vector for chimeric mouse/human APP carrying the Swedish mutation and a second for mutant PSEN1 (deltaE9) controlled by independent mouse prion protein promoter elements. The two transgenes co-integrated and co-segragate as a single locus. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity. Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing). Kinked tail phenotype that is believed to be due to genetic background. The Jackson Lab; available through the JAX MMRRC Stock# 034829 (formerly Jackson Lab Stock # 004462); Live Jankowsky et al., 2001, Jankowsky et al., 2004 Yes
NSE-APPsw Origin: C57BL/6 x DBA/2 APP APP KM670/671NL (Swedish) Transgene containing human APP (isoform 695) bearing the Swedish mutation under the control of neuron specific enolase (NSE) promoter. APP: Transgenic Alzheimer's Disease Increased Aβ42 in the cortex and hippocampus of 12 month old mice, but no plaques. Increased tau phosphorylation and TUNEL-stained nuclei relative to control mice. In water maze tests, 12 month old mice had longer escape latencies than age-matched control mice. Metallothionein expression was increased in brain astrocytes and was thought to attenuate Aβ-induced neurotoxicity.  Increased Cox-2 and caspase-3 compared to age-matched control mice.   Available through Yong K Kim Hwang et al., 2004 No
Knock-in of APP(V642I) Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice APP APP V717I (London) Targeted knock-in of the V642I mutation into exon 17 of the mouse APP gene using homologous recombination and the Cre-loxP system. APP: Transgenic Alzheimer's Disease Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy. At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels. Unknown Kawasumi et al., 2004 Yes
APPlon, APP-london, APPLd, APP-ld, APP(V717I), APP[V717I], APP.V717I, APP(London) (line 2), APP/LD/2 Tg(Thy1-APPLon)2Vln/0 Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP APP V717I (London) Transgene containing human APP (isoform 695) with the London mutation driven by the Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression. Increased mortality (72% by day 180). Increased incidence of seizures. Available through the KU Leuven Research and Development Office; the CRO reMYND offers research services with this line. Moechars et al., 1999 Yes
APPxPS1, APP(V717I)x PS1(A246E), APP[V717I]x PS1[A246E], APP.V717I x PS1.A246E Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-PSEN1*A246E)2Vln/0 Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP, PSEN1 APP V717I (London), PSEN1 A246E The transgene overexpresses the mutant human amyloid protein precursor APP (isoform 695), which bears the London (V717I) mutation, and human presenilin-1 with the A246E mutation, both under the control of the neuron-specific murine Thy1 promoter. APP: Multi-transgene; PSEN1: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression. The CRO reMYND offers research services with this line. Dewachter et al., 2000 Yes
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line Inbred C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic) A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. Cryopreserved. Contact Lennart Mucke Cheng et al., 2004 Yes
arcAbeta Origin: B6D2 F1 APP APP KM670/671NL (Swedish), APP E693G (Arctic) Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis. APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI. Unknown Knobloch et al., 2007 Yes
B6;CB-Tg(Thy1-PSEN1*M146V/Thy1-APP*swe)10Arte Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6 APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 M146V Co-integration of two transgenes, mutant APP carrying the K670N/M671L mutation, and mutant PSEN1 carrying the M146V mutation, both under the control of the Thy-1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. Good breeding capabilities and no premature death. Taconic: Stock #16347 Willuweit et al., 2009 Yes
BACE1fl/fl/UbcCreER X 5xFAD C57BL/6J Bace1, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5xFAD mice were crossed with Bace1fl/fl mice (Hu et al., 2018) to generate 5xFAD mice homozygous for a floxed Bace1 gene (“Bace1fl/fl/5xFAD). Bace1fl/fl/5xFAD mice were then bred to BACE1 conditional knock-out (Hu, Yan) mice. Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter. Normal contextual and cued fear conditioning, tested at 8 to 10 months of age. Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 10- to 12-month-old mice, but less severe than that seen in slices from control mice (5xFAD mice homozygous for a floxed Bace1 gene). Bace1fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Hu et al., 2018 Yes
Bace1 cKO, BACE1fl/fl;R26CreERT2-TAM C57BL6 Bace1 Mice in which exon 2 of Bace 1 is flanked by LoxP sites (Ou-Yang et al., 2018) were crossed with R26CreERT2mice (Ventura et al., 2007), which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus. Bace1: Conditional Knock-out Alzheimer's Disease Defects in axonal organization. Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations. BACE1fl/fl available through Robert Vassar; R26CreERT2 available through The Jackson Laboratory Stock# 008463, Live Ou-Yang et al., 2018 Yes
BACE1 cKO, BACE1fl/fl/UbcCreER C57BL/6J Bace1 These mice were generated by crossing Bace1fl/fl mice (Hu et al., 2018), in which exon 2 of the mouse Bace1 gene is flanked by loxP sites, with UBC-Cre-ERT2 mice (The Jackson Laboratory, Stock# 007001), which carry a transgene encoding Cre recombinase fused to a modified human estrogen receptor, driven by the ubiquitin C promoter. Bace1: Conditional Knock-out Alzheimer's Disease No gross morphological changes observed. BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age. Impaired long-term potentiation at Schaffer collateral–CA1 synapses in slices obtained from 10- to 12-month-old mice. Bace1fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. Hu et al., 2018 Yes
Bace1 cKO, BACE1fl/fl;CamKIIα-iCre C57BL6 Bace1 Mice in which exon 2 of Bace1 is flanked by LoxP sites (BACE1fl/fl) were crossed with mice carrying a transgene encoding Cre recombinase driven by the CamKIIα promoter (Casanova et al., 2001). Bace1: Conditional Knock-out Alzheimer's Disease Hypomyelination and defects in axon organization. Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments. Spontaneous behavioral seizures and epileptiform discharges in EEGs. BACE1fl/fl available through Robert Vassar;  CamKIIα-iCre available through the European Mouse Mutant Archive (EMMA) ID# EM: 01153, cryopreserved, sperm Ou-Yang et al., 2018 Yes
BACE1-/-, BACE1 KO B6.129-Bace1tm1Pcw/J C57BL/6J BACE1 Homologous recombination was used to disrupt a 2kb section of BACE1 containing exon 1 replacing it with a neomycin selection cassette and the HSV thymidine kinse gene. BACE1: Knock-Out Alzheimer's Disease Hypomyelination in the hippocampus and cerebral cortex, but normal axonal development. Increased thermal pain sensitivity as measured by a hot plate test. Decreased grip strength. Homozygous mice are viable, fertile, normal in size. No BACE1 protein is detected by Western blot. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs). The Jackson Lab: Stock# 004714; Live Cai et al., 2001 No
BACE2delta6, BACE2 KO B6;129P2-Bace2tm1Bdes/J Strain of origin: 129P2/OlaHsd BACE2 Cre mediated recombination was used to remove exon 6 of BACE2. A targeting vector containing a loxP site and hygromycin resistance gene flanked by FRT sites was introduced into intron 5 and a second loxP site was inserted within intron 6. Heterozygous mice were crossed with mice expressing Cre under the ubiquitous phosphoglycerate kinase promoter to delete exon 6 in progeny. BACE2: Knock-Out Alzheimer's Disease Not observed. Not observed. BACE2 deficient fibroblasts produced higher levels of Aβ compared with wild-type cells. The Jackson Lab: Stock# 005618; Cryopreserved Dominguez et al., 2005 No
BRI2-Aβ40 B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J B6C3, backcrossed to C57BL/6J to generate congenic strain Construct encodes a fusion protein of the BRI protein and Aβ40 driven by the mouse prion promoter; Aβ40 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ40. Transgenic Alzheimer's Disease No overt amyloid pathology or detergent-insoluble amyloid-β. Hemizygous mice on a mixed background (C57/B6//C3H) have intact cognition as measured by fear conditioning at 12 and 14-17 months. The Jackson Lab: Stock# 007180; Cryopreserved McGowan et al., 2005 No
BRI2-Aβ42, BRI-Abeta42 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J B6C3, backcrossed to C57BL/6J to generate congenic strain Construct encodes a fusion protein of the BRI protein and Aβ42 driven by the mouse prion promoter. Aβ42 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ42. Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss. On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid. The Jackson Lab: Stock# 007182; Cryopreserved McGowan et al., 2005 Yes
Brown, C9-BAC[GGGGCC]500 SJL/B6 C9orf72 Hexanucleotide repeat in C9ORF72 This transgenic mouse carries a bacterial artificial chromosome (BAC) containing exons 1 through 6 of human C9orf72 with ~500 GGGGCC repeat motifs and ~140.5 kb upstream. C9orf72: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Widespread RNA foci throughout the nervous system starting at 3 months of age, especially comprised of sense transcript. Dipeptide repeats (e.g., poly-GP) as soluble protein and insoluble aggregates. No neurodegeneration. No TDP-43 aggregation, gliosis, inflammation, or synapse loss. No overt behavioral abnormalities compared to non-Tg controls. Assessment included grip strength, Rotarod performance, and intruder test. Viable, fertile, born in Mendelian ratios. Available through Robert Brown Peters et al., 2015 Yes
Baloh/Lutz, C9-BAC[GGGGCC]100-1000, Tg(C9orf72_3) line 112, Line F112 C57BL/6J-Tg(C9orf72_i3)112Lutzy/J C57BL/6J C9orf72 Hexanucleotide repeat in C9ORF72 This transgenic mouse carries a bacterial artificial chromosome (BAC) containing full-length human C9ORF72 sequence with ~100-1000 repeats. C9orf72: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Widespread RNA foci throughout the nervous system first assessed at 3 months of age. Soluble dipeptide repeats (e.g., poly-GP) and insoluble aggregates. No neurodegeneration. No TDP-43 aggregation, gliosis, inflammation, or obvious synapse loss. No behavioral abnormalities compared to non-Tg controls at either young age (3 months) or advanced age (18 months). Tests included: grip strength, Rotarod performance, open-field, three-chamber, and Y-maze. Viable, fertile, born in Mendelian ratios. The Jackson Lab: Stock# 023099; Live O'Rourke et al., 2015 Yes
(G4C2)149, 149-repeat mice C57BL/6J C9orf72 Hexanucleotide repeat in C9ORF72 An adeno-associated viral (AAV) vector was used to deliver 149 repeats of the hexanucleotide GGGGCC motif, along with the 5' (119 bp) and 3' (100 bp) flanking regions of the C9ORF72 gene, driven by the β-actin promoter. Virus was injected into the lateral ventricles of wild-type pups on postnatal day 0. C9orf72: Virus Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Intranuclear foci containing antisense and antisense repeat RNA; cytoplasmic inclusions containing sense and antisense dipeptide repeat proteins; accumulation of phosphorylated TDP-43 and stress granule-associated proteins; neuron loss and gliosis. Motor and cognitive deficits emerge between 3 and 6 months of age. Hyperactivity seen by 3 months. Mislocalization of RanGAP1 suggests nucleocytoplasmic transport defects. Unknown. Chew et al., 2019 Yes
66-repeat mice, Petrucelli’s AAV C9 model C57BL/6 C9orf72 Hexanucleotide repeat in C9ORF72 An adeno-associated viral (AAV) vector was used to deliver a sequence of 66 repeats of the hexanucleotide, GGGGCC. The virus was injected into the cerebral ventricles of P0 pups. C9orf72: Virus Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Nuclear RNA foci in neurons, dipeptide aggregates (GA, GP, and GR), cytoplasmic inclusions of phosphorylated TDP-43, neuronal loss, brain atrophy, and gliosis. Subtle behavioral deficits including anxiety-like behavior, hyperactivity, and antisocial behavior. Subtle motor impairment and failure to improve on the Rotarod. Reduced body weight in females by 6 months. Viral construct available through Leonard Petrucelli Chew et al., 2015 Yes
C9orf72 KO, 3110043O21Rik Knock-out 3110043O21Riktm1(KOMP)Mbp C57BL/6N C9orf72 The mouse 3110043O21Rik gene (homologue of human C9orf72) was inactivated by deleting a region containing exons 2-6, which includes the start codon. The targeting vector contained expression cassettes, flanked by FRT sites, for lacZ and neo as selectable markers. C9orf72: Knock-Out Frontotemporal Dementia, Amyotrophic Lateral Sclerosis Chromatolytic structures are observed with H&E staining, in gray and white matter of the spinal cord. Neurodegeneration not present. Normal sensorimotor coordination and limb strength. Reduced activity in open-field test. Spleens and lymph nodes enlarged by 1 month, size increases with age. Histology shows enlarged debris-filled cells. Available through the UC Davis Knockout Mouse Project (KOMP) Repository, gene 3110043021Rik; Cryopreserved O'Rourke et al., 2016 Yes
CamKII-tTA;(GR)80 (line 16), CamKII;(GR)80 C57BL/6 CamKII-tTA;(GR)80 mice are produced by crossing a responder line carrying a (GGXCGX)80 sequence downstream of a tetracycline operon–responsive element (TRE) to an activator line expressing a tetracycline-controlled transactivator (tTA) under control of the CaMKIIα promoter. Bi-transgenic progeny constitutively express poly(GR) until transgene expression is suppressed by administration of the tetracycline analog doxycycline (DOX). Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Neuron loss in the frontal cortex, beginning between 3 and 6 months of age. Microgliosis and astrogliosis evident at 6 and 9 months, respectively. No TDP-43 inclusions seen in mice studied up to 8 months of age. DNA damage and mitochondrial abnormalities observed. Deficits in social behavior and increased anxiety emerge between 3 and 6 months. Working memory is intact at least through 9 months of age. Morphological defects in mitochondria seen in mice as young as 3 months of age. Disease-related phenotypes were prevented or reversed by reducing levels of poly(GR) in adult mice. Choi et al., 2019 Yes
CAST.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How CAST/EiJ APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with CAST/EiJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1. Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test). Available from The Jackson Laboratory, Stock #25973. Onos et al., 2019 Yes
APOE4/Trem2*R47H/Ceacam1 knock-out B6.Cg-Apoetm1.1(APOE*4)Adiuj Ceacam1em#1Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Ceacam1, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-out mutation of the Ceacam1 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Labortory Stock# 028709). APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available January, 2019 from The Jackson Laboratory, Stock# 030673 The Jackson Laboratory Yes
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Clasp2em1Adiuj Trem2em1Adiuj/J C57BL/6J Clasp2, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-in L163P mutation of the Clasp2 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available May, 2019 from The Jackson Laboratory, Stock# 031944 The Jackson Laboratory Yes
fPS1/fPS1Δ;Nestin-Cre (PS1 cKO) C57BL6/129 PSEN1 PS1 inactivation in neuronal progenitor cells (NPCs) and NPC-derived neurons and glia was achieved by crossing a floxed PS1 mouse with a Nestin-Cre transgenic mice. PSEN1: Conditional Knock-out Alzheimer's Disease Premature differentiation of neural progenitor cells results in reduced cells and neurons. 45 percent of late-born neurons fail to migrate to their appropriate positions in the superficial cortical layers. Gross behavior deficits. Mice are small. Premature death at 2-3 months of age. Available through Jie Shen Wines-Samuelson et al., 2005 No
APOE2-FAD, APOE2 Targeted Replacement x 5xFAD C57BL/6 APOE, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE2 Targeted Replacement mice were crossed with the 5xFAD line. APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice. 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE2 Targeted Replacement mice are available through Taconic, Stock# 1547-F or 1547-M. Youmans et al., 2012 Yes
APOE3-FAD, APOE3 Targeted Replacement x 5xFAD C57BL/6 APOE, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE3 Targeted Replacement mice were crossed with the 5xFAD line. APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice. 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE3 Targeted Replacement mice are available through Taconic, Stock# 1548-F or 1548-M. Youmans et al., 2012 Yes
APOE4-FAD, APOE4 Targeted Replacement x 5xFAD C57BL/6 APOE, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE4 Targeted Replacement mice were crossed with the 5xFAD line. APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.  Age-dependent learning and memory deficits in the Y maze and Morris water maze. 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE4 Targeted Replacement mice are available through Taconic, Stock# 1549-F or 1549-M. Youmans et al., 2012 Yes
B6(C3H)-Sod1m1H/J C57BL/6J SOD1 D83G in SOD1 This mouse has a point mutation (A>G) in the endogenous murine Sod1 gene, resulting from exposure to the chemical mutagen N-ethyl-N-nitrosourea (ENU). The endogenous murine Sod1 promoter drives expression of the mutant protein, which carries a D83G missense mutation. SOD1: Other Amyotrophic Lateral Sclerosis Upper and lower motor neuron loss in specific regions (layer V of motor cortex and lumbar spinal cord). Gliosis in spinal cord. Denervation of hindlimb muscle. Progressive motor impairments, including tremor, gait abnormalities, decreased grip strength, and impaired Rotarod performance. Liver tumors, kyphosis (hunched back), reduced body weight, loss of SOD1 activity. The Jackson Lab: Stock# 020440; Cryopreserved Joyce et al., 2015 Yes
FUSd14 B6C3F1 FUS FUS Δ14 Recombinant adeno-associated virus (AAV) to express mutant human FUS in the brain. Viral injection into the ventricles of P0 pups. Human FUS driven by the cytomegalovirus enhancer/chicken β-actin promoter. cDNA encodes C-terminal truncation, which lacks exon 14, and thus the entire nuclear localization signal. FUS: Virus Frontotemporal Dementia, Amyotrophic Lateral Sclerosis Widespread neuronal cytoplasmic inclusions (NCIs) by 3 months of age. Inclusions were FUS-positive and often co-labeled with ubiquitin.  No overt neurodegeneration or reactive gliosis. No overt motor phenotypes at 3 months of age. Viral construct available through Thomas Kukar Verbeeck et al., 2012 Yes
B6N;B6J-Fustm1Emcf/H C57BL6/J FUS FUSDelta14 truncation mutation The Fus gene in C57BL6/N mouse embryonic stem cells (ESC) was modified through homologous recombination using a targeting vector designed to introduce the following changes: g.13845 A>G (mutation at splice acceptor site of intron 13); g.14230 C>T, g.14232 A>T, g.14234C>G, g.14260 A>G, and g.14266 ATTA insertion, to humanize the coding sequence of exon 15. FUS: Knock-In Amyotrophic Lateral Sclerosis Progressive (not developmental) loss of lumbar spinal motor neurons, starting by 12 months of age; partial denervation of hindlimb muscles. Mislocalization of mutant FUS from nucleus to cytoplasm. Hindlimb motor impairment by 15 months. Premature death, beginning at 19 months of age. European Mouse Mutant Archive (EM:11106) Devoy et al., 2017 Yes
Fus-dNLS, Fus-deltaNLS, Fus-ΔNLS/+ C57Bl/6 Fus FUS ΔNLS A targeting vector encoding exons 13 and 14 of FUS followed by three stop codons and a poly A signal was inserted between exons 12 and 13 of FUS. These elements are flanked by a pair of loxP sites. Insertion of this transgene results in the exclusion of exon 15 and the NLS unless Cre-recombinase is expressed to excise the transgene. Fus: Knock-In Amyotrophic Lateral Sclerosis The spinal cord exhibited FusΔNLS mislocalization, a loss of motor neurons, and ubiquitin pathology. No impairments in grip strength or rotarod performance. Irregular walking patterns and reduced hang time on inverted grid test were observed. Altered electrical activity of the gastrocnemius or tibialis anterior muscles. Unknown. Scekic-Zahirovic et al., 2016, Scekic-Zahirovic et al., 2017 Yes
B6;SJL-Tg(Prnp-FUS*R521C)3313Ejh/J Transgene injected into B6SJL oocytes. Maintained on C57BL/6, therefore subsequent generations have a higher percentage of C57BL/6. FUS FUS R521C Transgene encoding human FUS with the R521C mutation near the C-terminus. Flag-tagged construct driven by the Syrian hamster prion protein promoter. FUS: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Robust neurodegeneration in the anterior horn of the spinal cord, including about 50% loss of neurons by end stage. Prominent microgliosis and astrogliosis in the anterior horn at end stage. Very rare cytoplasmic FUS inclusions. A variety of motor impairments from a young age, including spastic paraplegia, abnormal hindlimb clasping, gait abnormalities, and impaired performance on the Rotarod. Growth retardation, muscle atrophy, DNA damage, and RNA splicing defects. Males may be sterile. The Jackson Lab: Stock# 026406; Cryopreserved Qiu et al., 2014 Yes
APOE4 (line1)/APOE KO, Tg(GFAP-APOE*4)1Hol B6.Cg-Apoetm1Unc Cdh18Tg(GFAP-APOE_i4)1Hol/J. Formerly: B6.Cg-Tg(GFAP-APOE_i4)1Hol Apoetm1Unc/J B6/CBA; back-crossed onto C57BL6 background APOE Transgene of human APOE4 driven by the GFAP promoter; crossed to APOE knock-out mice. APOE: Transgenic; APOE: Knock-Out Alzheimer's Disease Developing and adult mice express human APOE4 in glia and neuropil. Unknown. Mice are viable, normal in size, and do not display any gross physical or behavioral abnormalities. The Jackson Lab: Stock# 004631; Cryopreserved Sun et al., 1998 No
hAbeta-loxP-KI on mixed B6J and B6NJ B6(SJL)-Apptm1.1Aduci/J mixed B6J; B6NJ APP Three point mutations were introduced into exon 14 (exon numbering according to APP695, with 16 exons) of the mouse App gene, to produce three amino acid substitutions within the Aβ sequence (amino acids 5 (G to R), 10 (F to Y) and 13 (R to H) of Aβ). Exon 14 is also flanked by loxP sites. APP: Knock-In Alzheimer's Disease Unknown. Unknown. Available February, 2019 from The Jackson Laboratory, Stock# 030898 The Jackson Laboratory Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem#1Adiuj Trem2em1Adiuj/J C57BL/6J APOE, APP, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the G601R, F606Y, and R609H (APP695 numbering) point mutations into the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, Jackson Lab Stock# 028709). APOE: Knock-In; APP: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available April, 2019 from The Jackson Laboratory, Stock# 030670 The Jackson Laboratory Yes
C57B6/C3H BACE1 Transgene of human BACE1 driven by the prion protein (PrP) promoter. BACE1: Transgenic Alzheimer's Disease No evidence of Aβ deposition in single transgenic animals. Unknown. Unknown Lee et al., 2005 No
C57BL/6 J BACE1 Wild-type human BACE driven by the murine Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Decreased levels of full-length mature APP and increased levels of C99 and C89. Human BACE mRNA 4x higher than endogenous murine BACE. Highest expression of human BACE protein in cortex and hippocampus, lowest in cerebellum. Available through Material Transfer Management at Novartis Bodendorf et al., 2002 No
B6(SJL)-Cr2tm1(CR2,CR1)How Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J Cr2, CR1, CR2, APOE, Trem2 TREM2 R47H This mutant line was generated by crossing APOE4/Trem2*R47H mice to mice in which the endogenous Cr2 gene was replaced with human CR1 and CR2 (The Jackson Laboratory Stock# 027713). Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available April, 2019 from The Jackson Laboratory, Stock# 031668 The Jackson Laboratory Yes
Tau-ON-hFUS-P525L C57Bl/6 FUS FUS P525L Transgene encoding myc-tagged human FUS-P525L with an upstream Lox-P flanked stop sequence was inserted into the MAPT locus by homologous recombination. These mice were crossed to the Prm1-Cre line for germline recombination to remove the stop sequence, allowing transgene expression. FUS: Knock-In Amyotrophic Lateral Sclerosis Progressive loss of spinal cord motor neurons associated with muscle denervation and reduced muscle fiber diameter. Gliosis in spinal cord. Abnormal mitochondrial morphologies. Mutant FUS mislocalized to cytoplasm. Deficits in wire hang test at 360 days. Progressive denervation of hind limb muscles. Unknown. Sharma et al., 2016 Yes
PrP-hFUS Tg (Prnp-FUS)WT3Cshw/J C57Bl/6/SJL founder mice backcrossed to C57Bl/6 FUS Transgene expressing wild-type human FUS with an N-terminal HA-tag. The mouse prion protein promoter (PrP) drives transgene expression. FUS: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia FUS accumulation in the cytoplasm, including cytoplasmic inclusions in neurons of the brain and spinal cord. Degeneration of spinal motor neurons (~60% by end stage) with astrogliosis and microgliosis. Severe motor impairment, starting as tremor and gait abnormalities, and progressing to impaired performance on the Rotarod and reduced locomotion. Ultimately hindlimb paralysis and inability to lift the pelvis. Born at Mendelian ratios. Focal muscle atrophy and signs of denervation in hindlimb muscles. Most founder lines did not propagate the transgene. The Jackson Lab: Stock# 017916; Cryopreserved Mitchell et al., 2012 Yes
Tau-ON-hFUS-R512C C57Bl/6 FUS FUS R521C Transgene encoding myc-tagged human FUS-R521C with an upstream Lox-P flanked stop sequence was inserted into the MAPT locus by homologous recombination. These mice were crossed to the Prm1-Cre line for germline recombination to remove the stop sequence, allowing transgene expression. FUS: Knock-In Amyotrophic Lateral Sclerosis Progressive loss of spinal cord motor neurons associated with muscle denervation. Gliosis in spinal cord. Mutant FUS mislocalized to cytoplasm. No data. Progressive denervation of hind limb muscles. Unknown. Sharma et al., 2016 Yes
PrP-PFN1-G118V C57Bl/6 PFN1 PFN1 G118V Untagged human PFN1-G118V cDNA is expressed by the mouse prion promotor (PrP). PFN1: Transgenic Amyotrophic Lateral Sclerosis Motor neuron loss in the spinal cord associated with muscle denervation and atrophy. Gliosis in spinal cord. Loss of corticospinal neurons of the motor cortex. Aggregates of TDP-43 in spinal motor neurons. Progressive motor impairments. Minor hind limb posture changes begin at 120 days. Paralysis occurred on average by 165-210 days. Denervation and atrophy of the gastrocnemius muscle in the hindlimb. Available through Mahmoud Kiaei Fil et al., 2017 Yes
human tau B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells that were subsequently injected into C57BL/6 blastocysts. The transgenic allele was generated in embryos derived from a cross between Swiss Webster and B6D2F1. Mice containing both alleles were back-crossed to C57BL/6 mice . MAPT Double mutant mice were generated by mating mice that express human tau (8c mice) (Duff et al., 2000), with tau knockout mice that have a targeted disruption of exon one of tau (Tucker et al., 2001), then back-crossed to obtain mice that are homozygous for disrupted murine MAPT while carrying the human tau transgene. MAPT: Knock-Out; MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss. Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009).  General health, weight, basic reflexes, sensory responses, locomotor function, anxiety level, and gross motor function were not different from age-matched controls (Polydoro et al., 2009). The Jackson Lab: Stock# 005491; Live. The CRO QPS-Austria offers research services with this line. Andorfer et al., 2003 Yes
CaMKII-tTA/TRE-hTau-A152T C57BL/6-Tg(tetO-MAPT*A152T)L1Lms/J C59Bl/6J MAPT MAPT A152T These bigenic mice use the CaMKIIα promoter to drive expression of tetracycline transactivator (tTA) in forebrain neurons. The responder transgene is the 1N4R isoform of human tau with the A152T mutation. Expression is constitutive unless suppressed by doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus. Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal. Increase in basal synaptic activity and epileptiform spikes. Life span normal. Available as single transgenics: The Jackson Lab Stock# 028979 (cyropreserved) and Stock# 007004 (live) Maeda et al., 2016 Yes
hTau40-AT, Ala152T-Tau, A152T-Tau, Tau/A152T C57BL/6 MAPT MAPT A152T Human full-length tau (hTau40) isoform 2N4R with the A152T mutation expressed under the Thy1.2 promotor is located in the ROSA26 locus. MAPT: Knock-In Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses. Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal. Increase in basal synaptic transmission. Available through Eva Mandelkow Decker et al., 2016, Sydow et al., 2016 Yes
Tau.P301S, hTAU[P301S], tau[P301S] Thy1-hTau.P301S (CBA.C57BL/6) CBAxC57BL/6 MAPT MAPT P301S Transgenic mice overexpressing a human tau isoform that is 383 amino acids long with four microtubule-binding repeat domains and without N-terminal inserts (4R/0N). Site-directed mutagenesis was used to introduce the P301S mutation. Transgene is under the control of the neuron-specific murine Thy-1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis. Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months. Muscle weakness, tremor. Frequent eye inflammation. Available for academic use from Michel Goedert and for commercial use from LifeArc. The CRO reMYND offers research services with this line. Allen et al., 2002 Yes
ΔNLS4; tTA/TDP-ΔNLS, TDP-43-ΔNLS, tTA/ΔNLS B6;C3-Tg(tetO-TARDBP*)4Vle/J Transgene injected into fertilized eggs from C57BL/6J x C3HeJ. TARDBP These bigenic mice use the CAMKIIα promoter to drive expression of tetracycline transactivator (tTA) in forebrain neurons. The responder transgene is wild-type human TDP-43 minus the nuclear localization signal (NLS). Human TDP-43 is expressed constitutively unless suppressed by doxycycline. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Severe neuronal loss and gliosis in the dentate gyrus and deep cortical layers. Only very rare cytoplasmic aggregates of TDP-43 despite high levels of cytosolic protein. Degeneration of the corticospinal tract, but no lower motor neuron loss or muscle atrophy. A variety of motor, cognitive, and social deficits, including abnormal clasping response, impaired coordination on the Rotarod, decreased grip strength, impaired recognition and spatial memory, and decreased social behavior. Cognitive and motor impairments largely reversible in young mice following short-term transgene suppression. Downregulation of endogenous mouse TDP-43. No change in mortality up to 7 months of age. Mendelian ratios of offspring. The Jackson Lab: Stock# 014650; Live Igaz et al., 2011 Yes
C57BL BACE1 Transgene expressing wild-type human BACE1 driven by the mouse Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Transgene expressed in neurons only. No change in processing of endogenous murine APP. No longer available through Michael Willem Willem et al., 2004 No
B6.Cg-Apoetm1.1(APOE*4)Adiuj Il1rapem#1Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Il1rap, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-out mutation of the Il1rap gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available January, 2019 from The Jackson Laboratory, Stock# 030304 The Jackson Laboratory Yes
PDGF-APPSw,Ind, PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20, hAPP, Mucke mice B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity. Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034836-JAX; Live Mucke et al., 2000 Yes
TauP301L-JNPL3 Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SW Mixed Background MAPT MAPT P301L Transgene for human MAPT (4R0N) with the P301L mutation driven by the mouse prion promoter. MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord. By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization. Eye irritiation, possibily due to carrying the Pde6brd1 retinal degeneration mutation carries Pde6brd1 mutation Taconic: Stock#2508 (homozygote), #1638 (heterozygote and wild-type) Lewis et al., 2000 Yes
B6(SJL)-Kif21bem1Adiuj Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J Kif21b, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-in T82T mutation of the Kif21b gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available May, 2019 from The Jackson Laboratory, Stock# 031938 The Jackson Laboratory Yes
C57BL/6-Lrrk2tm4.1Arte C57BL/6NTac LRRK2 LRRK2: Knock-In Parkinson's Disease Available through Taconic, Cat#13940, Live. Matikainen-Ankney et al., 2016 Yes
BAC Lrrk2-G2019S, FLAG-Lrrk2-G2019S, BAC-Lrrk2-G2019S, LRRK2 G2019S BAC Tg Mouse (Yue) B6.Cg-Tg(Lrrk2*G2019S)2Yue/J A BAC construct was injected into B6C3 F1 oocytes. Founder line 2 was established and maintained by breeding to C57BL/6J inbred mice. LRRK2 LRRK2 G2019S A bacterial artificial chromosome (BAC) containing the entire mouse Lrrk2 gene was modified to include the G2019S mutation. The BAC (~240 kb) contained the murine Lrrk2 promoter region (~35 kb) and a FLAG-tag downstream of the start codon. LRRK2: Transgenic Parkinson's Disease Brain appears normal. No neuronal or cell death at 12 months. No increase in α-synuclein or ubiquitin levels or aggregation. Decreased striatal dopamine content, decreased evoked release. Apparently normal behavior. No change in activity level or motor coordination at 12 months. Mutant Lrrk2 protein purified from mouse brain had increased kinase activity. Age-dependent electrophysiological changes in the hippocampus including increased basal synaptic efficiency though a postsynaptic mechanism and decreased LTD. Synaptic vesicle endocytosis impaired in cultured ventral midbrain neurons. Available through The Jackson Lab, Stock# 012467, Live. Li et al., 2010 Yes
G2019S-LRRK2 (line 340), G2019S-LRRK2 transgenic, LRRK2 G2019S Tg Mouse (Dawson/Moore) B6;C3-Tg(PDGFB-LRRK2*G2019S)340Djmo/J Transgene introduced into C57BL/6J x C3H/HeJ embryos. Founder mice were bred with C57BL/6J mice. LRRK2 LRRK2 G2019S Transgenic mice overexpress full-length mutant human LRRK2 with the G2019S mutation. Transgene expression is driven by a hybrid CMVe-PDGFβ promoter. LRRK2: Transgenic Parkinson's Disease Age-dependent dopaminergic neuron degeneration in the substantia nigra. No reduction in striatal dopaminergic terminals or dopamine levels. No evidence of abnormal protein accumulation even at advanced ages. Abnormal mitochondria in striatal neurons and microglia, and accumulation of autophagic vacuoles. Activated striatal microglia; CD68 and TNF-α levels increased in whole brain.  Deterioration of Rotarod performance in 14- to 18-month-old mice. No change in pre-pulse inhibition of the acoustic startle reflex. Anxiety/depression-like symptoms at 10-12 months. No differences in body weight or survival. Reduced serotonin levels in the hippocampus at 10-12 months. Age-dependent increase in 5-HT1a receptors in the hippocampus, amygdala, and dorsal raphe nucleus. Available through The Jackson Laboratory, Stock# 016575, Cryopreserved. Ramonet et al., 2011 Yes
R26-LRRK2; R26-LRRK2+/+, R26-LRRK2+/+/DAT-Cre mice, ROSA26-LRRK2(R1441C), R1441C LRRK2 Tg Mouse (Moore) STOCK Gt(ROSA)26Sortm1(LRRK2*R1441C)Djmo/J R26-LRRK2 mice were generated from 129/SvJ ES cells microinjected into C57Bl/6J mouse blastocysts. Chimeras were bred with C57Bl/6J mice and maintained on a mixed genetic background (129/SvJ and C57Bl/6J). BAC-DAT-iCRE mice were maintained on a C57Bl/6J background. LRRK2 LRRK2 R1441C Full-length human LRRK2 with the R1441C mutation was targeted to the endogenous ROSA26 locus by homologous recombination. Cre-mediated excision of the transcriptional termination sequence allows for transgene expression. The Cre line expressed Cre-recombinase driven by the dopamine transporter (DAT) promoter derived from a BAC construct containing the entire mouse DAT (slc6) gene. LRRK2: Transgenic Parkinson's Disease No neurodegeneration in the brain. No proteinaceous inclusions of α-synuclein, ubiquitin, or tau. No reactive gliosis. No change in dopamine levels. Subtle morphological abnormalities in neuronal nuclei, including altered nuclear envelope. No overt behavioral differences. Activity levels and Rotarod performance are normal into advanced age. Fertile. Normal survival. No overt olfactory deficits. Available through The Jackson Laboratory, Stock# 022793, Cryopreserved. Tsika et al., 2014 Yes
WT-OX, LRRK2 WT BAC, WT LRRK2 Mouse (BAC Tg), WT LRRK2 BAC Tg Mouse (Li) FVB/N-Tg(LRRK2)1Cjli/J BAC injected into fertilized FVB zygotes. Founder mice bred with FVB/N inbred mice for many generations, and then with FVB/NJ inbred mice. LRRK2 A 188 kb human bacterial artificial chromosome (BAC) containing the entire human LRRK2 gene, with 29 kb upstream and 42 kb downstream. LRRK2: Transgenic Parkinson's Disease Overtly normal brain structure. Intact neurites. No observed behavioral differences from wild-type mice at 10 months of age. Available through The Jackson Laboratory, Stock# 009610, Live. Li et al., 2009 Yes
MAPT KI, hTau KI C57BL/6J MAPT Homologous recombination was used to replace the entire genomic sequence of murine Mapt (from exon 1 to exon 14) with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region (H2 haplotype; NCBI Reference Sequence: NG_007398). MAPT: Knock-In Alzheimer's Disease, Other Tauopathy No evidence of increased neuroinflammation, neuronal death, or brain atrophy in MAPT knock-in mice, compared with wild-type mice. MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory. Compared with wild-type mice, MAPT knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain. Available through Takaomi Saido, RIKEN Center for Brain Science. Saito et al., 2019, Hashimoto et al., 2019 Yes
B6(SJL)-Mthfrem1Adiuj Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J Mthfr, APOE, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the A262V mutation into the Mthfr gene of APOE4/Trem2*R47H mice—double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene. Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available March, 2019 from The Jackson Laboratory, Stock# 030922 The Jackson Laboratory Yes
line 13 C57BL/6 x DBA/2F1, crossed with DBA MAPT MAPT L266V, MAPT G272V Transgene expressing human 3R tau bearing the L266V and G272V mutations under the neuronal mThy-1 promoter. MAPT: Transgenic Frontotemporal Dementia, Pick's disease, Alzheimer's Disease Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology. Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test. Increased anxiety. Unknown Rockenstein et al., 2015 Yes
TASD41, Line 41, hAPPSL, hAPP-SL, AβPP751, mThy1-hAβPP751 Swe Lon (line 41), APP751SL, hAPPlon/swe line 41, APP41 mThy1-hAβPP751 Swe Lon C57BL/6 x DBA APP APP KM670/671NL (Swedish), APP V717I (London) The transgene over-expresses the mutant human amyloid protein precursor (751 isoform), which bears both the Swedish (K670N/M671L) and the London (V717I) mutations, under the control of the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region. Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration. Available through Eliezer Masliah. The CRO PsychoGenics offers research services with this line. Rockenstein et al., 2001 Yes
rNLS8, regulatable NLS B6;C3-Tg(NEFH-tTA)8Vle Tg(tetO-TARDBP*)4Vle/J NEFH-tTA mice and tetO-hTDP-43ΔNLS line 4 mice were maintained on a mixed C57BL/6J x C3HeJ background. TARDBP These bigenic mice are the progeny of NEFH-tTA transgenic mice, in which the neurofilament heavy chain promoter drives expression of tetracycline transactivator (tTA), and tetO-hTDP-43ΔNLS (line 4) mice, which express a form of human TDP-43 lacking the nuclear localization signal in a tTA-dependent manner. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Widespread cytoplasmic inclusions of TDP-43 in the brain and spinal cord. Ubiquitin-positive inclusions, loss of endogenous mouse nuclear TDP-43, cortical atrophy, motor neuron loss, astrogliosis, and NMJ denervation. A variety of motor impairments, including hindlimb clasping, fine tremor in forelimb and/or hindlimb, progressive loss of grip strength, and decline in coordinated movement and balance. Progressive decrease in body mass from a peak two weeks off dox. Atrophy of hindlimb muscles at end-stage. Premature death (median survival 10.3 weeks off dox). Available through The Jackson Lab as single transgenics: Stock# 025397 and Stock# 014650; Live. See also double transgenic Stock# 028412; Live Walker et al., 2015 Yes
dNLS-FUS, deltaNLS-FUS C57Bl/6J FUS FUS ΔNLS Transgene encoding myc-tagged human FUS with a C-terminal truncation to delete the nuclear localization signal. Expression driven by the Thy1.2 promoter. FUS: Transgenic Amyotrophic Lateral Sclerosis The motor cortex exhibited gliosis, a loss of neurons, and ΔNLS-FUS aggregates positive for ubiquitin and p62.  Progressive motor impairments by 12 weeks. Mice demonstrated tremors, limb clasping, gait abnormalities, as well as impaired performance on the Rotarod and hanging wire test. Reduced lifespan. Available through Daisuke Ito. Shiihashi et al., 2016 Yes
ΔNLS-FUS x TARDBP, deltaNLS-FUS x TAR4 C57Bl/6J FUS, TARDBP FUS ΔNLS A cross between the ΔNLS-FUS and TDP-43(WT) mice. The ΔNLS-FUS line contains a transgene expressing myc-tagged human FUS lacking the nuclear localization signal, driven by the Thy1.2 promoter. The TDP-43(WT) line contains a transgene that encodes wild-type human TARDBP, driven by the Thy-1 promoter. FUS: Transgenic; TARDBP: Transgenic Amyotrophic Lateral Sclerosis The motor cortex exhibited gliosis, a loss of neurons, and DNLS-FUS aggregates positive for ubiquitin and p62.  Progressive motor impairments by 8 weeks. Mice demonstrated tremors, limb clasping, gait abnormalities, as well as impaired performance on the Rotarod and hanging wire test. Reduced lifespan. Available through Daisuke Ito. Shiihashi et al., 2016 Yes
Origin: C57BL/6J; backcrossed with murine APOE-null mice APOE ApoE3 minigene driven by the rat neuron-specific enolase promoter. APOE: Transgenic Alzheimer's Disease Human ApoE3 protected against the age-dependent neurodegeneration seen in APOE -/- mice. Unknown. Widespread neuronal expression of ApoE in the brain. Expression of ApoE3 protected against kainic acid-induced neuronal damage (loss of synaptophysin-positive presynaptic terminals and MAP2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus). Available through Robert Mahley Raber et al., 1998 No
Origin: C57BL/6J; backcrossed with murine ApoE-null mice APOE The ApoE4 minigene driven by the rat neuron-specific enolase promoter. APOE: Transgenic Alzheimer's Disease Not observed. NSE-ApoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and seen primarily in females. Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against kainic acid-induced neuronal damage. Available through Robert Mahley Raber et al., 1998 No
JU.Tg(NSE-APP751)Cordell JU (Developed by Eric Bradford at University of California, Davis) APP Transgene expresses wild-type human APP751 isoform under the control of the rat neural-specific enolase (NSE) promoter. APP: Transgenic Alzheimer's Disease Age-dependent increase in Aβ deposits and tau immunoreactivity. Learning and memory deficits are age-dependent as assessed on spontaneous alternation in a Y maze and in the water-maze task. Extinct Quon et al., 1991 Yes
C57BL/6× DBA/2 PSEN2 PSEN2 N141I (Volga German) Transgene containing human PSEN2 carrying the N141I mutation driven by the neuron-specific enolase (NSE) promoter. PSEN2: Transgenic Alzheimer's Disease Not observed. Behavioral deficits in the water maze at 12 months in mice expressing mutatnt as well as wild-type PSEN2, including longer escape latencies than wild-type mice, but no difference in swimming speed. Expression of PSEN2 was higher in mice expressing mutant as well as wild-type PSEN2 compared to age-matched, non-transgenic mice. Alterations in levels of Aβ42, caspase-3 and Cox-2 proteins. Unknown Hwang et al., 2002 No
PARK2-Q311X, Parkin-Q311X(A), Parkin-Q311X (line A), Parkin Q311X BAC Tg Mouse (Yang) FVB/NJ-Tg(Slc6a3-PARK2*Q311X)AXwy/J The BAC was microinjected into fertilized FVB/NJ zygotes, then bred to FVB/NJ inbred mice. PRKN (parkin) Parkin Q311X Bacterial artificial chromosome (BAC)-mediated expression of mutant parkin in dopaminergic neurons. The promoter and regulatory regions of Slc6a3 (dopamine transporter) drive expression of parkin with the truncation mutation Q311X. The protein has an N-terminal Flag-tag. Two copies of the transgene integrated in tandem. PRKN (parkin): Transgenic Parkinson's Disease Degeneration of dopaminergic neurons in the substantia nigra and nerve terminals in the striatum. Reduced dopamine in the striatum. Accumulation of proteinase-K resistant α-synuclein and oxidative protein damage. Late-onset hypoactivity (about 16 months of age), other modest changes in motor behavior and coordination in tests that included traversing a beam or removing adhesive. Available through The Jackson Laboratory, Stock# 009090, Live. Lu et al., 2009 Yes
hAPP695Indiana, elan mouse, PDAPP, PD-APP C57B6 x DBA2 APP APP V717F (Indiana) A PDGF-driven human APP minigene with the V717F (Indiana) mutation. The construct contained APP introns 6-8 allowing alternative splicing of exons 7 and 8. APP: Transgenic Alzheimer's Disease Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus. Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months. Alterations in sleep/wake states, thermoregulation, and motor activity.   Unknown Games et al., 1995, Rockenstein et al., 1995 Yes
APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months. Unknown. Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition. Available through Lennart Mucke Hsia et al., 1999 No
line I5 B6.Cg-Tg(PDGFB-APP)5Lms/J (C57BL/6 x DBA/2)F2 APP APP-WT driven by the human PDGF-β promoter; an APP transgene with the Indiana mutation was converted to wild-type by PCR primer modification. APP: Transgenic Alzheimer's Disease Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months. Unknown. The Jackson Lab: Stock# 004662; Cryopreserved Mucke et al., 2000 Yes
Thy1.2-PFN1C71G/Prp-PFN1C71G FVB/N-Tg(Prnp-PFN1*C71G)22Zxu Tg(Thy1-PFN1*C71G)67Zxu/J FVB/NJ PFN1 PFN1 C71G Human PFN1-C71G cDNA with an N-terminal V5 tag is expressed by the human Thy1.2 promotor or mouse prion promotor (Prp). The mouse is homozygous for Thy1.2-PFN1-C71G and hemizygous for Prp-PFN1-C71G. PFN1: Multi-transgene Amyotrophic Lateral Sclerosis Motor neuron loss in the spinal cord associated with muscle denervation and atrophy. Gliosis in spinal cord. No neuronal loss in the cortex but neurodegeneration in medulla. Aggregates of PFN1, ubiquitin, and p62 form in motor neurons. Progressive motor impairments. Minor gate changes start by 4 month. Paralysis occurred on average by 7 months.Progressive decrease in body weight. Progressive decrease in body weight. Available as a triple transgenic through The Jackson Lab, Stock# 028608 Yang et al., 2016 Yes
Pink1-, Pink1-deficient mouse, PARK6 mouse, Pink1-/-, PINK1 G309D (PINK1-) KI Mouse (Auburger) B6;129-Pink1tm1Aub/J The vector was introduced into a 129/SvEV-derived embryonic stem cell line. Resulting chimeric mice were bred and maintained on a pure 129 background. PINK1 Pink1 G309D A targeting vector was used to introduce the G309D mutation into exon 4 at the orthologous mouse locus. A floxed neomycin cassette in the inverse orientation was inserted into intron 5 via homologous recombination. PINK1: Knock-In Parkinson's Disease No neuronal loss. No Lewy bodies or α-synuclein aggregates, but alpha-synuclein expression change in brainstem/midbrain. Low dopamine levels. Mitochondrial dysfunction (e.g., reduced ATP, reduced respiratory activity). Increase in factors involved in toll-like receptor signaling in the cerebellum, and increased astrocytic and microglial markers in the corticospinal tract and striatum. Reduced spontaneous locomotor activity in open-field test. No difference in strength or coordination. Electrophysiological abnormalities, including altered glutamergic activity in midbrain dopaminergic neurons and early hypersynchrony in motor cortex. Medium spiny neurons in striatal slice exhibit giant GABAergic currents. Hyperactive subthalamic nucleus neurons, indicated by spontaneous bursts instead of single spikes. Subtle alterations in gene expression in cerebellum, midbrain, and striatum. Available through The Jackson Laboratory, Stock# 013050, Cryopreserved. Gispert et al., 2009 Yes
Pink1 KO, Pink1 knockout mouse, Pink1-, Pink1-/-, PINK1 KO Mouse (Shen) B6.129S4-Pink1tm1Shn/J Congenic C57BL/6J. The construct was introduced into 129S4/SvJae-derived J1 embryonic stem cells, which were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to generate homozygotes and then backcrossed to C57BL/6J for >7 generations. PINK1 A targeting vector containing a PGK-Neo cassette was used to disrupt exons 4 through 7 of the endogenous PINK1 gene. This creates a nonsense mutation at the beginning of exon 8; truncated RNA is degraded. PINK1: Knock-Out Parkinson's Disease Overtly normal brain structure. Normal numbers of dopaminergic neurons and tyrosine hydroxlase levels in substantia nigra at 8-9 months of age. Alterations in the dendrites of midbrain dopaminergic neurons and cultured cortical neurons. Altered shape, density, and movement of dendritic mitochondria in cultured primary neurons from embryonic mice. Reduced spontaneous locomotor activity and skill at 3-6 months. Modest vocalization deficits at 4-6 months. Heavier than wildtype mice at 5 months. Plasticity abnormalities: reduced LTP and absent LTD in response to high frequency stimulation; reversed by dopamine agonists. Abnormal rise in serum cytokines in response to exhaustive exercise which acutely stresses mitochondria. Available through The Jackson Laboratory, Stock# 017946; Live. Kitada et al., 2007 Yes
hAPP/hTau/hPS1, PLB1(Triple) C57BL6 APP, MAPT, PSEN1 APP V717I (London), APP KM670/671NL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W Targeted insertion of human APP and tau sequences at the HPRT site on the X chromosome, driven by mouse CaMKII-α. Human APP (isoform 770) with the Swedish and London mutations. Human tau (isoform 2N/4R, 441 amino acids) with P301L and R406W. APP/tau-expressing animals (PLB1-double) were crossed with hPS1 (A246E) transgenic mice (Borchelt et al., 1997) to generate the triple transgenic. APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene Alzheimer's Disease Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep. Available through Bettina Platt Platt et al., 2011 Yes
hBACE1 C57BL/6J, for at least six generations BACE1 Targeted insertion of a single copy of human BACE1 at the HPRT locus on the X chromosome. Transgene expression driven by the mouse CaMKII-α promoter. BACE1: Transgenic Alzheimer's Disease Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology. Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety. Breeding, litter size, and overall health are normal. Reduced body weight in knock-in animals after six months of age in males and nine months in females. Available through Bettina Platt Plucińska et al., 2014 Yes
Plcg2 knock-out B6(SJL)-Plcg2em2Adiuj/J C57BL/6J Plcg2 CRISPR/Cas9 was used to introduce a knock-out mutation into the mouse Plcg2 gene. Plcg2: Knock-Out Alzheimer's Disease Unknown. Unknown. Available Fall, 2018 from The Jackson Laboratory, Stock# 29910 The Jackson Laboratory Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Plcg2em2Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Plcg2, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the p.M28L mutation (methionine to leucine at position 28) into the Plcg2 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available March, 2019 from The Jackson Laboratory, Stock# 030674 The Jackson Laboratory Yes
APP(Prnp), line A-2 B6.Cg-Tg(Prnp-APP)A-2Dbo/J C57BL/6 APP Transgene expresses human APP driven by the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Unknown. Unknown. Jackson Labs: Stock# 006006; Cryopreserved The Jackson Laboratory No
PrP-hFUS*R495X transgenic line PX78, PrP-hFUS(R495X) line PX78 B6.Cg-Tg(Prnp-FUS*R495X)78Ljh/J Construct microinjected into C57BL/6 x SJL)F2 hybrid embryos and founders bred to FVB for 4+ generations. Subsequently back-crossed at JAX to create a C57BL/6 congenic. FUS FUS R495X These mice express a mutant form of human FUS carrying a truncation mutation near the C-terminus. The transgene is driven by the mouse prion protein promoter (Prp). The mutation abrogates the nuclear localization sequence and leads to cytoplasmic mislocalization of FUS. FUS: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Cytoplasmic mislocalization of human FUS, but no cytoplasmic inclusions or signs of neuronal loss. No overt behavioral abnormalities. By 8-12 months, EMG detected hindlimb muscular abnormalities including fibrillation potentials, muscle denervation, and a reduction in the number of motor units. Congenic available through The Jackson Lab: Stock# 019728; Cryopreserved Tibshirani et al., 2015 Yes
PWT17, PrP-hFUS(WT) line PWT17 B6.Cg-Tg(Prnp-FUS)17Ljh/J Construct microinjected into C57BL/6 x SJL)F2 hybrid embryos and founders bred to FVB for 4+ generations. Subsequently back-crossed at JAX to create a C57BL/6 congenic. FUS These mice overexpress wild-type human FUS. The transgene is driven by the mouse prion protein promoter (PrP). FUS: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia No overt neuropathology. Predominantly nuclear FUS. No inclusions or over neuronal loss. No overt behavioral abnormalities prior to becoming moribund around 203 days of age. Unexplained premature lethality about 203 days of age, proceeded by less than a week of ill-health. Congenic available through The Jackson Lab: Stock #020783; Cryopreserved Tibshirani et al., 2015 Yes
Tg(Thy1-PSEN1*A246E)2Vln/0 FVB/N PSEN1 PSEN1 A246E Transgene human PSEN1 with the A246E mutation driven by the mouse Thy1 promoter. PSEN1: Transgenic Alzheimer's Disease Histologically normal up to 2 years old by hematoxylin-eosin, silver, and thioflavin-S staining. Learning and spatial memory were unaffected in the water maze test. Neither the escape latency nor escape pathway was different from PSEN1 wild-type mice at 1 and 9 months of age. Mice are more sensitive to kainic acid displaying greater KA-induced seizure activity and neuronal damage. LTP induced by a strong stimulus was not altered, but a weak stimulation at synapses between Schaeffer’s collaterals and CA1 pyramidal neurons elicited LTP only in mutant mice. No longer available through Paul van Dun Schneider et al., 2001 No
PS1cKO, PSEN1 conditional KO fPS1/fPS1;αCaMKII-Cre CaM-Cre tg mice were generated in C57BL/6J x CBA hybrid, and then back-crossed several generations to C57BL/6J. The floxed PS1 mouse was generated in C57BL/6J and 129/Sv hybrid. PSEN1 PS1 conditional KO mice with selective deletion of PSEN1 in excitatory neurons of the forebrain beginning about 1 month of age post-natally were generated by crossing a floxed PS1 mouse with a CamKII-Cre transgenic mouse. PSEN1: Conditional Knock-out Alzheimer's Disease Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments. Subtle but significant deficits in long-term spatial memory in the Morris water maze. Available through Jie Shen Yu et al., 2001 Yes
PSEN1(M146L), PS1 (M146L) line 5.1 B6/D2/Swe/SJL mixed background PSEN1 PSEN1 M146L (A>C) Transgene containing human PSEN1 with the M146L mutation driven by the rat PDGF-β promoter. PSEN1: Transgenic Alzheimer's Disease No abnormal pathology up to 2.5 years. Elevated Aβ2(43); no effect on Aβ40. Altered mitochondrial activity. Disregulation of calcium homeostasis. No difference from wild-type mice in the “Y” maze (alternation performance or activity) at 12-14 weeks. Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with wild-type mice. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection. Available through the Technology Transfer Office, Patents & Licensing, University of South Florida. The CRO PsychoGenics offers research services with this line. Duff et al., 1996 No
PSEN1(M146V) (line 8.9) Swiss Webster x B6D2F1 PSEN1 PSEN1 M146V Transgene containing human PSEN1 with the M146V mutation driven by the rat PDGF-β promoter. PSEN1: Transgenic Alzheimer's Disease No abnormal neuropathology up to 2.5 years. Elevated Aβ42(43). Altered mitochondrial activity and disregulation of calcium homeostasis. Unknown. Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with nontransgenic or mice transgenic for wild-type PSEN1. Available through the Technology Transfer Office, Patents & Licensing, University of South Florida Duff et al., 1996 No
PS-1 P264L knock-in R1 line of the ES cells (129 mouse strain) PSEN1 PSEN1 P264L An exon replacement strategy was used to generate mouse lines carrying a targeted mutation in their endogenous presenilin-1 gene. A proline-to-leucine substitution was targeted to codon 264 in exon 8 by homologous recombination in embryonic stem (ES) cells. Cre-lox system to remove the neomycin selection cassette from the targeted gene. PSEN1: Knock-In Alzheimer's Disease Not observed. Unknown. Unknown Siman et al., 2000 No
B6.PS2APP, TG B6.PS2APP mice (line B6.152H) Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz C57BL/6 APP, PSEN2 APP KM670/671NL (Swedish), PSEN2 N141I (Volga German) Coinjection of two transgenes into C57/Bl/6 zygotes: Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter and human APP751 with the Swedish mutation driven by the Thy1.2 promoter. APP: Transgenic; PSEN2: Transgenic Alzheimer's Disease Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. Decreased survival of newborn neurons in the dentate gyrus at about 4 months. Reduced endoplasmic reticulum Ca2+ and calcium dysregulation. A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of 10 month old animals compared to wild-type mice. Decreased perfusion in the occipital cortex at all ages tested (10-17 months). Available through Laurence Ozmen Ozmen et al., 2009 Yes
PS2(N141I) x APPswe , hPS2(N141I) x hAPPswe Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr C57BL/6, DLB/2, crossed to C57BL/6 APP, PSEN2 APP KM670/671NL (Swedish), PSEN2 N141I (Volga German) Double transgenics created by crossing APPSwe mice (transgene containing the 751 isoform of human APP with the Swedish mutation driven by the Thy1.2 promoter) with PS2(N141I) mice (tansgene containing human PSEN2 with the N141I mutation driven by the mouse prion protein promoter). APP: Transgenic; PSEN2: Transgenic Alzheimer's Disease Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months. Loss of metabotropic glutamate receptors (mGlu2) in certain brain regions of aged mice as demonstrated by autoradiography. Available through Laurence Ozmen Richards et al., 2003 Yes
Prp-huPS2(N141I), PS2-N141I (line 30), hPS2mut Tg(Prnp-PSEN2*N141I)30Jgr Originally generated in a B6.D2 background, then crossed into C57BL/6J. PSEN2 PSEN2 N141I (Volga German) Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter. PSEN2: Transgenic Alzheimer's Disease Unknown. Unknown. Ubiquitous expression of mutant transgene. Brain homogenate from 2 week-old mice had PSEN levels 1.8-2.2 fold higher than wild-type mice. Disrupted Ca2+ homeostasis, similar to that of double transgenic PS2APP mice, including a reduction in endoplasmic reticulum Ca2+ content in cultured neurons and a generally decreased response to metabotropic agonists. Available through Laurence Ozmen Richards et al., 2003 No
PS1 + APP, PSAPP, APP/PS1, APP/PS1 double transgenic B6/D2/Swe/SJL mixed background APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 M146L (A>C) These double transgenic mice were generated by crossing mice overexpressing human APP with the Swedish mutation driven by the hamster prion protein gene promoter (the Tg2576 model) with mice overexpressing human PSEN1 with the M146L mutation driven by the PDGF-β promoter (PSEN1(M146L), line 5.1). The two transgenes segregate independently. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter,  cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. Selective increase in brain Aβ42(43) in the double transgenics (41% increase at 6 weeks) compared to Tg2576 single transgenic, which had unchanged Aβ40 and Aβ42(43) at this age. Tg2576: Taconic (Stock #001349) and Charles River; PS1(M146L): University of South Florida Technology Transfer Office. The CRO PsychoGenics offers research services with Tg2576 and the double transgenic line. Holcomb et al., 1998 Yes
PS1/PS2 cDKO, PSEN1/PSEN2 conditional double knock-out fPS1/fPS1;αCaMKII-Cre;PS2-/- C57BL6/129 hybrid PSEN1, PSEN2 To generate forebrain-specific conditional double knockout mice lacking both PS1 and PS2 (PS cDKO) mice, floxed PS1 (fPS1), αCaMKII-Cre transgenic mice and PS2-/- mice were crossed together to obtain fPS1/fPS1;αCaMKII-Cre;PS2-/- mice. PSEN1: Conditional Knock-out; PSEN2: Knock-Out Alzheimer's Disease At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus. Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age. Increased neurogenesis in the dentate gyrus. Available through Jie Shen Saura et al., 2004 Yes
PS1 conditional KO B6;129P-Psen1tm1Vln/J Origin: 129P2/OlaHsd; backcrossed to C57BL/6 PSEN1 A targeting vector containing a neomycin resistance gene was inserted downstream of exon 7 of PSEN1; loxP sites were inserted on both sides of exon 7 and downstream of the neomycin resistance gene. PSEN1: Knock-Out Alzheimer's Disease No morphological abnormalities. When crossed with Cre recombinase driven by Thy1, brain levels of Aβ40 and Aβ42 decrease and C-terminal fragments of APP accumulate. When crossed with Cre recombinase driven by Thy1, no cognitive deficit in an object recognition task. When crossed with Cre recombinase driven by Thy1, LTP induction is slightly altered. The Jackson Lab: Stock# 007605; Cryopreserved Dewachter et al., 2002 No
PS1-/-, PS1-, PSEN1 null, Psen1tm1Shn, PS1 null B6.129-Psen1tm1Shn/J C57BL/6 PSEN1 A targeting construct containing a neomycin cassette was used to disrupt exons 2 and 3 of the endogenous mouse PS1 gene. PSEN1: Knock-Out Alzheimer's Disease Impaired neurogenesis. Massive neuronal loss. Hemorrhages in the CNS. Unknown. Homozygous mice die shortly after birth; heterozygous mutants are viable and fertile. Gross skeletal malformations. The Jackson Lab: Stock# 003615; Cryopreserved Shen et al., 1997 No
PS1M146V KI, PS1M146VKI, The Miles W. Miller Mouse B6.129-Psen1tm1Mpm/J C57BL/6 PSEN1 PSEN1 M146V Point mutations were introduced into exon 5 of the endogenous mouse PSEN1 gene altering the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. The targeting vector contained a lox-P flanked neomycin resistance cassette and herpes simplex virus thymidine kinase genes. PSEN1: Knock-In Alzheimer's Disease Hypersensitive to kainate-induced degeneration and death of CA3, CA1 and hilar neurons. Cultured hippocampal neurons have increased vulnerability to death induced by glutamate. Disrupted calcium homeostasis. Increased oxidative stress and mitochondrial dysfunction. Unknown. Mice are viable, fertile, and normal in size. No gross physical or behavioral abnormalities. The Jackson Lab: Stock# 004193; Cryopreserved Guo et al., 1999 No
line 13, PS1(P117L) Mixed C57BL/6 and DBA/2J PSEN1 PSEN1 P117L Transgene of human PSEN1 with the P117L mutation driven by the neuron specific enolase (NSE) promoter. PSEN1: Transgenic Alzheimer's Disease No plaques or diffuse amyloid deposits at 2-3 months. Elevated generation of Aβ42. Unknown. Express human PSEN1 at 2-3x the level of endogenous murine PSEN1. Impaired neurogenesis in the hippocampus. No longer available Wen et al., 2002 No
PS1(WT), PSEN1 (wild-type) Mixed C57BL/6J, DBA/2J PSEN1 Human wild-type PSEN1 driven by neuron-specific enolase (NSE). PSEN1: Transgenic Alzheimer's Disease No pathological changes have been observed in these mice. Unknown. No longer available Wen et al., 2002 No
line G9, H163R mutant PS-1 YAC, B6-G9, PS1-YAC B6.129S4-Tg(PSEN1H163R)G9Btla/J Origin: 129S4/SvJae, backcrossed to C57BL/6 PSEN1 PSEN1 H163R A 1000 kb YAC transgene (788H12) containing the entire human PSEN1 gene with the H163R mutation. Transgene also has ~550 kb of upstream and 350 kb of downstream flanking sequences. PSEN1: Transgenic Alzheimer's Disease Elevated Aβ42 in the brain and plasma. Higher levels and earlier Aβ deposition when crossed with APP YAC line R1.40. Unknown. Alternatively spliced human PSEN1 transcripts. The Jackson Lab: Stock# 006469; Cryopreserved Lamb et al., 1999 No
PS2-/-, PSEN2 null, PSEN KO, PS2 null B6.129P-Psen2tm1Bdes/J 129P2/OlaHsd derived embryonic stem cells injected into C57BL/6 blastocysts; resulting chimeric mice backcrossed to C57BL/6J PSEN2 A targeting vector containing a hygromycin resistance gene driven by the phosphoglycerate kinase promoter was used to disrupt exon 5 of PSEN2 by introducing a frame shift between exons 4 and 6. PSEN2: Knock-Out Alzheimer's Disease No gross brain abnormalities or astrogliosis. Unknown. Alveolar wall thickening, pulmonary fibrosis, mild hemorrhage in the lungs. The Jackson Lab: Stock# 005617; Cryopreserved Herreman et al., 1999 No
PWK.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How PWK/PhJ APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with PWK/PhJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques and plaque-associated gliosis by 8 months. Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze. Available from The Jackson Laboratory, Stock #25971. Onos et al., 2019 Yes
APPNLI 129S6FVB F1 APP APP KM670/671NL (Swedish), APP V717I (London) These are bigenic mice with the CAMKII-α promoter driving expression of tetracycline transactivator (tTa) in excitatory neurons in the forebrain, and a responder transgene consisting of mutant human APP (isoform 695) carrying the Swedish and London mutations. The expression of the transgene is constitutive until suppressed by doxycycline. APP: Transgenic Alzheimer's Disease Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers. No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests. Reduced body weight at 24-27 months relative to non-Tg littermates and those expressing only tTA. Available through Karen Ashe Liu et al., 2015 Yes
neuropsin-tTA x FVB-Tg(tetO-tauP301L)4510 4510 mice are on an FVB background. Neuropsin-tTA mice are on a C57BL/6 background. MAPT MAPT P301L Bigenic mice made by crossing an activator line, neuropsin-tTA, with a responder line, Tg(tetO-tauP301L)4510. The neuropsin promoter drives the tetracycline transactivator (tTA) transgene preferentially in a subset of entorhinal neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bigenic mice is constitutive until suppressed by doxycycline. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss. Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test. No apparent change in anxiety as assessed by the open field test. Reduced Arc induction in the hippocampus after contextual fear conditioning. Subtle differences in basal synaptic transmission with enhanced axonal excitability. de Calignon et al., 2012 Yes
rTg4510, rTg(tetO-TauP301L)4510, Tau P301L 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; Fgf14Tg(tetO-MAPT*P301L)4510Kha/J. Formerly: 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ Mixed: 129S6 (activator) X FVB (responder) MAPT MAPT P301L Bi-transgenic mice are made by crossing an activator line, CaMKIIα-tTA, with a responder line, Tg(tetO-tauP301L)4510. The CaMKIIα promoter drives the tetracycline transactivator (tTA) transgene preferentially in forebrain neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bi-transgenic mice is constitutive until suppressed by doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau. Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved. Homozygous mice are not viable. It should be noted that disruption of an endogenous mouse gene, caused by random insertion of the MAPT transgene, significantly contributes to the neuropathological and neurodegenerative phenotypes observed in rTg4510 mice 4510 responder line: The Jackson Lab: Stock# 015815; Activator line: The Jackson Lab: Stock# 016198. Santacruz et al., 2005, Ramsden et al., 2005, Gamache et al., 2019 Yes
Tau R406W-Prp C57BL6 x C3H, maintained in B6C3 background MAPT MAPT R406W Human tau with the R406W mutation driven by the mouse prion protein promoter. MAPT: Transgenic Frontotemporal Dementia Age-dependent increase in tau. Neurofibrillary-tangle-like pathology (filamentous intraneuronal tau aggregates), especially in the hippocampus. Neurodegeneration. Extensive gliosis in the brain and spinal cord. Progressive motor weakness with advancing age, as demonstrated by dystonic movements of the hindlimbs when lifted by the tail. Altered microtubule binding and slow axonal transport of tau. Reduced lifespan. Unknown Zhang et al., 2004 No
SAMP8, SAMP-8, SAM-P/8, SAM-P8 AKR/J, suspected outbreeding to unknown line One of several related strains developed from an AKR/J inbred line with a spontaneous accelerated aging phenotype. Spontaneous Alzheimer's Disease Age-associated increase in hippocampal Aβ from 4 to 12 months, but no plaque-like structures by Congo red or thioflavine S. Spongiform degeneration: vacuoles of various size in the neuropil in the brain stem. Microglial cell proliferation. Degeneration of dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus. Age-associated behavioral impairments including learning and memory difficulties, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythms of spontaneous motor activity and drinking behaviours. Envigo (formerly Harlan): SAMP8-TaHsd Yagi et al., 1988 No
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Snx1em1Adiuj Trem2em1Adiuj/J C57BL/6J Snx1, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a D465N mutation in the Snx1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available May, 2019 from The Jackson Laboratory, Stock# 031942 The Jackson Laboratory Yes
line 29, SOD1 (G37R) (hybrid background), G37R(29) SOD1, SOD1 G37R C57BL/6J x C3H/HeJ)F2 SOD1 SOD1 G37R Transgene carrying a 12kb DNA fragment encoding human SOD1 with the G37R mutation. Transgene driven by the human SOD1 promoter. SOD1: Transgenic Amyotrophic Lateral Sclerosis Degeneration of motor neurons in the spinal cord and brainstem characterized by extensive vacuolization. Astrogliosis. Wallerian degeneration of large myelinated axons. No overt upper motor neuron loss. Progressive motor impairment, beginning with reduced spontaneous movement, then tremors, limb weakness, poor grooming, and muscle wasting. Eventual paralysis of hindlimbs. Elevated dismutase activity in the brain and spinal cord (~7-fold). Unknown Wong et al., 1995 Yes
SOD1 (G85R) (line 148) Transgene injected into hybrid (C57BL/6J x C3H/HeJ)F2 embryos. SOD1 These transgenic mice express human SOD1 with the G85R substitution. 12 kb DNA sequence under the control of the human promoter and regulatory elements. SOD1: Transgenic Amyotrophic Lateral Sclerosis Degeneration of lower motor neurons, especially large-caliber axons, but also loss of motor neurons in the ventral horn. Extensive glial pathology in the spinal cord, including astrogliosis and microgliosis. Abundant SOD1 inclusions in astrocytes. Progressive motor impairment generally starting around 8 months of age with reduced grip strength in one hindlimb, rapidly spreading to other limbs and leading to paralysis. Unknown status of the hybrid line. A congenic line is available through The Jackson Lab: Stock# 008248; Cryopreserved Bruijn et al., 1997 Yes
G1H, High-copy SOD1-G93A, B6SJL.SOD1-G93A, Tg(hSOD1-G93A)1GUR mice, Gurney mice B6SJL-Tg(G93A-SOD1)1Gur/J C57Bl/6/SJL. SOD1 SOD1 G93A These transgenic mice express multiple copies of human SOD1 bearing the missense mutation G93A randomly integrated into chromosome 12 of the mouse. SOD1: Transgenic Amyotrophic Lateral Sclerosis Neuronal loss in the spinal cord (~50% loss in cervical and lumbar segments by end stage). Degeneration of upper motor neurons and brainstem nuclei. Swollen neurites, Gallyas silver-positive aggregates, vacuoles, and neuritic spheroids. Gliosis. Axonal degeneration and denervation of NMJ. Progressive motor impairment that starts as a shaking tremor. Proximal muscle weakness along with muscle atrophy, eventually leading to paralysis and death. Weight loss. The mutant SOD1 retains enzymatic activity. The Jackson Lab: Stock# 002726; Live Gurney et al., 1994, Chiu et al., 1995 Yes
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Sorl1em1Adiuj Trem2em1Adiuj/J C57BL/6J Sorl1, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-in A528T mutation of the Sorl1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Available May, 2019 from The Jackson Laboratory, Stock# 031940 The Jackson Laboratory Yes
hm2α-SYN-39, HM2, hm2α-SYN, human doubly mutated α-synuclein, A30P/A53T aSyn Mouse (Tg), A30P/A53T aSyn Tg Mouse (Richfield), alpha-synuclein A30P/A53T Mouse (Tg), B6J(239) C57BL/6J-Tg(Th-SNCA*A30P*A53T)39Eric/J Transgene injected into C57/BL6 oocytes, then bred to C57/BL6J. SNCA SNCA A30P, SNCA A53T This model expresses a transgene encoding human α-synuclein with two mutations (A30P and A53T) driven by 9kb rat tyrosine hydroxylase (TH) promoter. SNCA: Transgenic Parkinson's Disease Progressively loss of dopaminergic neurons in the substantia nigra pars compacta, observed by 8.5 months. No α-synuclein inclusions. Morphological abnormalities in the dopaminergic system, including axonal and dendritic abnormalities, reduced dopamine concentration in the striatum. More active as young adults, then hypoactive compared to non-Tg. Also reduced motor coordination in old age as measured by the time to right from an inverted wire screen. No weight differences compared to non-Tg. Available through The Jackson Laboratory, Stock# 008239, Live. Richfield et al., 2002 Yes
G2-3(A53T), PrPsynA53T, A53TαS Tg mice (line G2-3), MoPrP-Huα-Syn(A53T), Hualpha-Syn(A53T), A53T aSyn Tg Mouse (Lee), alpha-synuclein A53T Mouse (Tg) B6.Cg-2310039L15RikTg(Prnp-SNCA*A53T)23Mkle/J. Formerly: B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J Established as C3H/HeJ x C57BL6/J hybrids, then maintained by backcrossing to C57Bl6/J. SNCA SNCA A53T Transgene comprising human α-synuclein with the A53T mutation was inserted downstream of the mouse prion protein (PrP) promoter. SNCA: Transgenic Parkinson's Disease No overt neuronal loss. Alterations in dopaminergic-associated proteins in the striatum, substantia nigra, and nucleus accumbens. Region-specific neuronal accumulation of fibrillar α-synuclein, ubiquitin, and neurofilament-H, and accompanying astrocytosis. Early hyperactivity followed by severe motor impairment, manifesting as wobbling, posturing, decreased spontaneous locomotor behavior, inability to navigate the Rotarod, and ultimately paralysis and death. At 11–12 months, spatial memory impaired as assessed by the Barnes circular maze. Premature death, defects in hippocampal synaptic function. Available through The Jackson Laboratory, Stock# 006823, Live. Lee et al., 2002 Yes
PAC-Tg(SNCA-A53T) +/+; Snca-/-, dbl-PAC-Tg(SNCAA53T);Snca-/-, A53T aSyn Tg Mouse (Nussbaum), Alpha-synuclein A53T Mouse (Tg) on SNCA KO FVB;129S6-Sncatm1Nbm Tg(SNCA*A53T)1Nbm Tg(SNCA*A53T)2Nbm/J The PAC transgene was injected into FVB/N oocytes and founder mice bred to FVB/N. The knockout mice were made in a 129S6/SvEvTac background. SNCA SNCA A53T In this double-transgenic model, one parental line expresses mutant human α-synuclein (A53T mutation) via a 146 kb P1 artificial chromosome (PAC) containing full-length human SNCA gene and 34 kb upstream sequence. The other line is an Snca knockout line generated by replacing exons 4 and 5 with a neomycin resistance cassette. SNCA: Transgenic; SNCA: Knock-Out Parkinson's Disease No loss of dopaminergic neurons in the substantia nigra by 18 months of age. Rare dystrophic synapses in the hippocampus at advanced age, but no Lewy body-like pathology or α-synuclein aggregation in the brain. No change in striatal dopamine concentration. Impaired performance on the Rotarod and reduced spontaneous locomotor activity in open-field test. Gastrointestinal dysfunction (e.g., reduced fecal mass, reduced colonic motility, prolonged whole-gut transit time). α-synuclein–positive aggregates in enteric nervous system. No difference in body weight. No olfactory deficits. No difference in autonomic regulation of heart rate. Available through The Jackson Laboratory, Stock #010799; Live. Kuo et al., 2010, Cabin et al., 2002 Yes
Snca KO, Snca -/-, Snca KO Mouse (Nussbaum), Alpha-synuclein KO Mouse Inbred 129/SvEvTac background. SNCA The mouse Snca gene was disrupted using a targeting vector that replaced exons 4 and 5 with the neomycin resistance gene. SNCA: Knock-Out Parkinson's Disease No gross brain abnormalities. Electron microscopy revealed synaptic vesicle abnormalities in hippocampal neurons, i.e., fewer vesicles in the reserve pool. Behavior is largely normal. Normal performance on the Rotarod. Subtle differences in locomotor activity (e.g., less rearing) but normal overall distance travelled. Learning and memory appear intact. Possible anxiety-like phenotype. Microglial abnormalities. Reduced cardiolipin content in the brain. Some mitochondrial abnormalities. Unknown. Cabin et al., 2002 Yes
Sncaflox(neo), SNCAflox delta neo, Snca conditional knockout, SNCA KO Mouse (Buchman), Alpha-synuclein KO Mouse (Conditional) B6(Cg)-Sncatm1.1Vlb/J C57BL/6J SNCA A targeting vector containing a FRT site-flanked neomysin cassette and a loxP site was inserted downstream of exon 2 and another loxP site was inserted upstream of exon 2. Flp-mediated recombination removed the FRT-flanked neo cassette, leaving exon 2 floxed. When bred to Cre-expressing mice, the resulting offspring have the first coding exon deleted in Cre-expressing tissues. SNCA: Conditional Knock-out Parkinson's Disease No data. No data. Available through The Jackson Laboratory, Stock #025636, Live. Ninkina et al., 2015, Roman et al., 2017 Yes
Prp-TDP43A315T B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J C57BL/6J x CBA mice backcrossed to C57BL/6J. TARDBP TARDBP A315T This transgenic mouse expresses full-length human TARDBP with an N-terminal Flag tag and the A315T mutation. The transgene is driven by the mouse prion protein (PrP) promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis Minimal motor neuron loss in the spinal cord and cortex (but see Espejo-Porras et al., 2015 and Zhang et al., 2016). Ubiquitin-positive aggregates in upper and lower motor neurons. Rare TDP-43 aggregates. Astrocytosis in spinal cord and cortical layer V. Hyperexcitability of somatostatin interneurons. Axonal degeneration and ~ 20% loss of NMJ innervation (gel diet). Variable. Gait abnormalities, and impaired performance on the Rotarod. Also deficits in radial arm water maze, not due to deficits in swimming speed. Behavior potentially confounded by gut phenotype.  Severe dysfunction in the intestinal tract involving degeneration of neurons in the colon resulting in reduced motility though the ileocaecal area. GI obstruction is the likely cause of death unless the diet is modified with soft food or gel diet. The Jackson Lab: Stock# 010700; Live Wegorzewska et al., 2009, Hatzipetros et al., 2014 Yes
Baloh’s TDP-43, C57BL/6-CBA TDP-43 A315T The Prp-TDP43A315T transgene was introduced into oocytes from C57BL/6J x CBA mice. TARDBP TARDBP A315T Transgene encodes full-length, human, mutant TARDBP with the A315T mutation and an N-terminal Flag tag. The mouse prion protein (PrP) promoter drives transgene expression. TARDBP: Transgenic Amyotrophic Lateral Sclerosis Upper and lower motor neuron loss. Cytoplasmic aggregates of ubiquitinated proteins in motor neurons. Cortical gliosis. No cytoplasmic aggregates of TDP-43. Gait abnormalities around three months, developing into a characteristic “swimming gait” by four to five months. Born at normal Mendelian ratios. Grossly normal up to three months. Muscle pathology at end-stage, including atrophic muscle fibers. Generally milder phenotypes in females. No longer available on a C57BL/6J x CBA background Wegorzewska et al., 2009 Yes
C57BL/6J Tardbp Tardp Q331K CRISPR/Cas9 was used to introduce the p.Q331K mutation into the mouse Tardp gene. Tardbp: Knock-In Frontotemporal Dementia, Amyotrophic Lateral Sclerosis Unknown. Unknown. Available through Pietro Fratta or Abraham Acevedo-Arozena Fratta et al., 2018 Yes
LCDmut Tardbp M323K DBA/2J x C57BL/6J Tardbp Tardbp M323K This line was generated after screening DNA archives from two large-scale chemical mutagenesis projects (Acevedo-Arozena et al., 2008; Gondo et al., 2010) for mutations in Tardbp. Tardbp: Other Frontotemporal Dementia, Amyotrophic Lateral Sclerosis At 18 months of age, p62- and ubiquitin-positive inclusions in the ventral regions of the spinal cord, although apparently not in the cytoplasm of motor neurons. TDP-43 normally localized to the nucleus in 12-month mice. At 24 months, a 28 percent reduction in the number of motor neurons in the sciatic motor neuron pool, compared with control littermates. Grip strength in both male and female mice begins to decline at 12 months of age. By 24 months, there is a nearly 40 percent reduction in force measured in tibialis anterior muscles and a 15 percent reduction in motor units innervating the extensor digitorum muscle. Mice from original founders, on a hybrid DBA/2J x C57BL/6J background, are available from the RIKEN BioResource Center, BRC# GD000110. Fratta et al., 2018 Yes
RRM2mut Tardbp F210I DBA/2J x C57BL/6J Tardbp Tardp F210I This line was generated after screening DNA archives from two large-scale chemical mutagenesis projects (Acevedo-Arozena et al., 2008; Gondo et al., 2010) for mutations in Tardbp. Tardbp: Other Frontotemporal Dementia, Amyotrophic Lateral Sclerosis No spinal motor neuron loss, no p62- or ubiquitin-positive inclusions at 2 years in heterozygotes. Grip strength normal at 2 years in heterozygotes. Homozygous mutation is embryonic lethal. Muscle force, motor unit numbers normal at 2 years in heterozygotes. Mice from original founders, on a hybrid DBA/2J x C57BL/6J background, are available from the RIKEN BioResource Center, BRC# GD000108. Fratta et al., 2018 Yes
thy1-APPswe Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6 APP APP KM670/671NL (Swedish) Transgene expresses human APP (isoform 695) harboring the Swedish mutation, driven by the murine Thy-1 promoter. APP: Transgenic Alzheimer's Disease Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes. Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning. No differences in body temperature, locomotor activity, or Rotarod performance, relative to non-Tg controls. Unknown Richardson et al., 2003 Yes
TAS10 x TPM, APPswe x PS1.M1466V, TAS/TPM TAS10 transgene originally injected into C57BL/6 x C3H oocytes, with some backcrossing to C57BL/6. TPM generated on pure C57BL/6 background. APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 M146V This is a double transgenic model generated by crossing TAS10 mice (an APP transgenic line expressing human APP695 with the Swedish mutation) with TPM mice (a PSEN1 transgenic expressing human PSEN1 with the M146V mutation). Both transgenes are driven by the murine Thy-1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology. Age-dependent impairment in object recognition memory starting around 6 months of age.  Unknown Howlett et al., 2004 Yes
Tau(WT) transgenic (line 264) B6C3F1 embryos, backcrossed to C57BL/6 MAPT This transgenic mouse expresses 3-repeat (3R) and 4-repeat (4R) isoforms of wild-type human tau. The minigene, driven by the mouse CAMKIIα promoter, includes intronic sequences flanking exon 10, allowing for physiological splicing of exon 10. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy No overt neuropathology even at the advanced age of 24 months. Comparable to non-Tg mice in Morris water maze tasks at 4 and 6 months of age. Available through Hiroshi Mori and Takami Tomiyama Umeda et al., 2013 No
C57BL/6 (75%) and 129/Ola (25%). MAPT A fragment of human tau (187-441 a.a.) expressed under control of the human tau promotor was inserted at the Hprt locus. MAPT: Transgenic Progressive Supranuclear Palsy, Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Progressive tau pathology in the hippocampus, including abnormally phosphorylated and misfolded tau, mislocalized tau, and tangle-like structures. Dystrophic neurites. Impaired spatial learning and memory in the Morris water maze. Early motor impairments, including abnormal limb clasping, Rotarod deficits and decreased grip strength. Muscle fibers in the quadriceps and latissimus muscles appeared to be degenerative/regenerative. Progressive spine curvature. Unknown. Bondulich et al., 2016 Yes
B6.Cg-Tg(Thy-MAPT*)2652Gds C57BL/6J MAPT This transgenic mouse overexpresses wild-type human tau (1N4R). The Thy1.2 promoter drives high levels of transgene expression in the CNS. MAPT: Transgenic Frontotemporal Dementia, Other Tauopathy, Alzheimer's Disease Extensive pretangle pathology throughout the brain (e.g. phospho- tau) but no mature neurofibrillary tangles and only mild oligomeric tau, restricted to the CA1 region of the hippocampus. Dystrophic neurites and axonal pathology (spheroids). No overt neuronal loss. Motor deficits develop with age, including decreased grip strength and impaired Rotarod performance. Cognitive deficits, indicative of impaired spatial learning and memory, as assessed by the Barnes maze. Homozygous mice have reduced body weight, reduced fertility, and premature death. Some homozygous mice also exhibit seizure activity. The MMRRC Stock# MMRRC:036717 Wheeler et al., 2015 Yes
Tau 10 + 16 , Tau(10+16 intron mutation)Tg, line 609 B6C3F1 embryos, backcrossed to C57BL/6 MAPT MAPT IVS10+16 C>T This model expresses a tau minigene driven by the mouse CAMKIIα promoter. The minigene encodes human tau 441, including partial intronic sequences flanking exon 10 of MAPT. The intronic mutation, IVS10 +16 C>T, was introduced by site-directed mutagenesis. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease, Other Tauopathy Aggregated tau in neurons of the entorhinal cortex, hippocampus, and cerebral cortex at advanced ages. Intraneuronal accumulation of tau oligomers in the hippocampus. Neuronal loss in the entorhinal cortex and hippocampus. Gliosis. Some hippocampal areas affected by age-related synaptic dysfunction and reduced synaptic density. Impaired spatial reference memory as measured by the Morris water maze by 6 months of age.  Human tau transcripts containing exon 10 are over-represented in the adult mouse brain, leading to elevated levels of 4R tau relative to 3R tau. Available through Hiroshi Mori and Takami Tomiyama Umeda et al., 2013 Yes
TauA152T-AAV C57BL/6 MAPT MAPT A152T An adeno-associated viral (AAV1) vector encoding TauA152T under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice. MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice. Compared with GFP-AAV controls, TauA152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. TauA152T-AAV mice also exhibited motor impairment on the Rotarod. Unknown. Carlomagno et al., 2019 Yes
Transgenic caspase-cleaved tau BALB/C MAPT These transgenic mice express a truncated form of human tau (0N4R) that lacks the last 20 acids of the C-terminus, thus recapitulating the tau fragment produced by caspase cleavage (TauC3). Expression in the brain is driven by the promoter of the angiogenesis inhibitor 1 associated protein 4 (BAI1-AP4) gene. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia No significant cell loss or astrogliosis in the brain. Age-dependent reduction in synaptic proteins (e.g. synaptophysin, PSD95) by 1.3 to 3 months of age. Hyperphosphorylated tau oligomers and aggregates. Learning and memory deficits by 1.3 to 3 months of age, as assessed by the Y-maze and passive avoidance tests. No significant motor impairment. Normal lifespan. Unknown Kim et al., 2016 Yes
mTau-E10-KO Mixed background (BALB/c x C57B1/B6 x B6D2F1) MAPT Gene-targeted deletion of exon 10 in murine tau gene. MAPT: Knock-Out Alzheimer's Disease, Frontotemporal Dementia No overt neuropathology at 12 months of age. Age-dependent deterioration of sensorimotor functions, including coordination deficits on the Rotarod and a decrease in muscle strength. No deficits in learning or memory. Humanized splicing pattern of murine tau, leading to the production of 3R tau rather than 4R tau. No anxiety phenotype. Mice are no longer available, but frozen ES cells are available through Lars Nilsson or Astrid Gumucio Gumucio et al., 2013 No
"Proaggregation mutant", TauΔK, hTau40Δ280 Unknown. MAPT MAPT K280del These are bigenic mice in which the TET-OFF system is used to temporally control human tau expression in the brain. Tetracycline transactivator (tTA) is downstream of the CAMKII-α promoter, driving expression in excitatory neurons in the forebrain. tTA in turn stimulates expression of the responder transgene, full-length human tau (hTau40, 2N4R) carrying the FTD-associated deletion, ΔK280. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Abundant pre-tangle pathology, but only rare mature tangles, and only at advanced ages. Tau pathology included mislocalization of tau to the somatodendritic compartment, aggregation, and hyperphosphorylation. Unknown. Available through Eva Mandelkow. Eckermann et al., 2007 Yes
Tau.P301L, hTau.P301L, Tau-4R-P301L, Tau(P301L) Thy1-hTau.P301L FVB/N MAPT MAPT P301L These transgenic mice overexpress the human Tau-4R/2N isoform bearing the P301L mutation under the control of the neuron-specific murine Thy1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF. Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months. Premature death around 8-12 months, preceded by weight loss, hyperkyphosis, reduced activity, and upper airway dysfunction. The CRO reMYND offers research services with this line.  Terwel et al., 2005 Yes
TauP301L-AAV C57BL/6 MAPT MAPT P301L An adeno-associated viral (AAV1) vector encoding TauP301L under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice. MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age. Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age. Unknown. Cook et al., 2015 Yes
Line PS19, PS19Tg B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J (C57BL/6 x C3H)F1 MAPT MAPT P301S Transgenic line expressing mutant human tau under the direction of the mouse prion protein (Prnp) promoter. The transgene codes for tau with four microtubule-binding domains and one N-terminal insert (4R/1N). MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis. Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months. Clasping and limb retraction when lifted by the tail at three months, followed by limb weakness and brain atrophy. Homozygous females do not mate. The Jackson Lab: Stock# 008169; Live. Research with this model is available from QPS Austria. Yoshiyama et al., 2007 Yes
Triple transgenic, 3Tg B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) C57BL/6, DBA/2; backcrossed to C57BL/6 APP, MAPT, PSEN2 APP KM670/671NL (Swedish), MAPT P301L, PSEN2 N141I (Volga German) PS2APP mice (line B6.152H) x tau mice (line B6.TauP301L). PS2APP were generated by co-injecting two transgenic constructs: human PSEN2 (N141I mutation) and human APP (Swedish mutation) driven by the mouse prion promoter and the mouse Thy1 promoter respectively. The transgenic TauP301L mouse (line pR5) expresses the human tau40 isoform driven by the Thy1.2 promoter. APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic Alzheimer's Disease Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology. Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and ROS compared to wild-type. No differences in APP expression, APP cleavage or Aβ accumulation compared to PS2APP. Levels of ptau422 increased in an age-dependent manner, but levels of ptau231 did not. Available through Laurence Ozmen Grueninger et al., 2010 Yes
TgTauR406W, Tau R406W-CAMKII B6SJL/F1; backcrossed to C57BL/6J MAPT MAPT R406W Human 4-repeat tau cDNA with the R406W mutation containing myc and FLAG tags at N-and C-terminal ends, respectively, and driven by the CaMK-II promoter. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments. Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits. No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests).  Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality. Unknown Tatebayashi et al., 2002 Yes
“Proaggregation mutant”, TauRDΔ, TauRD, TauRD/ΔK280, TauRDΔK C57BL/6 MAPT MAPT K280del Regulatable expression of an abbreviated human tau sequence (amino acids 244-372) encompassing the four microtubule-binding repeat domains and carrying the ΔK280 mutation. Transgene is driven by the forebrain-specific CAMKIIα promoter. TET-OFF system in which the transgene is regulated by the tetracycline transactivator (tTA) and turned off by administration of doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss. Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance. Missorting of tau into the somato-dendritic compartment. Calcium dysregulation at synaptic boutons. Deficits in synaptic plasticity, including LTP and LTD. Unknown Mocanu et al., 2008 Yes
MAPT V337M, Tg214 B6SJL/F1 MAPT MAPT V337M (Seattle) Human 4-repeat tau driven by the PDGF-β promoter. Tagged with myc and Flag on the N- and C-terminals respectively. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure. Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze. The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels. In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response. Unknown Tanemura et al., 2002, Tanemura et al., 2001 Yes
Truncated beta-amyloid 42 C57BL6 APP Transgenic vector expresses a human N-terminally truncated Aβ sequence (3-42) fused to thyrotropin-releasing hormone. The transgene is under the control of the murine Thy1.2 regulatory sequence. The glutamate at position 3 of Aβ was mutated to glutamine to facilitate pyroglutamate formation by the enzyme glutaminyl cyclase. APP: Transgenic Alzheimer's Disease Intraneuronal accumulation of Aβ peptides in the hippocampus by 3 months and in cerebellar nuclei by 6 months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits. Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 or 6 months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at 3 and 6 months as indicated by the balance-beam test, but impairment at 12 months. Available through Thomas Bayer Wittnam et al., 2012 Yes
Transgene injected into C3H x C57Bl/6 embryos and then crossed with C57Bl/6. TARDBP TARDBP A315T Full-length human TDP-43 with the A315T mutation introduced by site-directed mutagenesis. The transgene is driven by the endogenous human promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Cytoplasmic inclusions of TDP-43, axonal changes, gliosis, no overt neuronal loss or loss of axons. Increased levels of cytotoxic 25 kDA C-terminal fragment of TDP-43. Age-associated cognitive and motor deficits as measured by the passive avoidance test and the Rotarod. Normal lifespan and fertility. Available through Jean-Pierre Julien Swarup et al., 2011 Yes
line 23 STOCK Tg(Prnp-TARDBP*A315T)23Jlel/J Transgene injected into fertilized hybrid B6SJLF1oocytes. Founders bred with CD1 to create hybrid CD1 and B6SJLF. TARDBP TARDBP A315T Transgene encodes full-length human TDP-43 with the A315T mutation. The mouse prion protein (Prp) promoter drives transgene expression. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia No overt neuronal loss in the brain or spinal cord. Ubiquitin-positive cytoplasmic inclusions in neurons of the ventral horn and brainstem. Astrocytosis. Cytoplasmic aggregates of TDP-43 are largely absent, although some phospho-TDP-43 inclusions at end-stage. Progressive motor impairment characterized by weakness, a decline in grip strength, and reduction in stride length. Weakness was usually more pronounced in the hindlimbs. Prior to motor deficits, mice exhibit increased fat storage, decreased lean muscle mass, and larger adipocytes in white fat. The Jackson Lab: Stock# 016143; Cryopreserved Stallings et al., 2010 Yes
Transgene injected into C3H x C57Bl/6 embryos. Founders backcrossed with C57Bl/6. TARDBP TARDBP G348C Full-length human TDP-43 with the G348C mutation introduced by site-directed mutagenesis. The transgene is driven by the endogenous human TARDBP promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Cytoplasmic inclusions of TDP-43 in neurons, axonal changes, denervated NMJs, gliosis, no overt neuronal loss or loss of axons. Increased levels of cytotoxic 25 kDA C-terminal fragment of TDP-43. Age-associated cognitive and motor deficits as measured by the passive-avoidance test, the Barnes maze, and the Rotarod. Impaired recovery after crush injury to the sciatic nerve (e.g., delayed recovery of motility and reduced axon regrowth). Normal lifespan and fertility. Available through Jean-Pierre Julien Swarup et al., 2011 Yes
TDP-43 M337V PrP (line 4) C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J Transgene injected into fertilized C57BL/6 oocytes. Founders bred with B6. TARDBP TARDBP M337V Transgene expresses full-length human TARDBP with the M337V mutation, driven by the mouse prion protein (PrP) promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia No overt neuronal death. Microgliosis and astrogliosis. Abnormal mitochondria in the form of eosinophilic aggregates in spinal motor neurons. Widespread ubiquitination and accumulation of phospho-tau. Body tremors and gait difficulties before one month of age, leading to a “dragging” gait. An inability to right themselves precipitating euthanasia around one to two months of age. Reduced brain and body weight compared with non-Tg littermates. The Jackson Lab: Stock# 017604; Cryopreserved Xu et al., 2011 Yes
Mt-TAR6/6 Transgene injected into BL6/SJL oocytes. Founders crossed to C57BL6/J. TARDBP TARDBP M337V The Thy-1.2 promoter drives expression of a transgene encoding human TARDBP with the M337V mutation. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Neuronal loss in cortical layer V motor neurons, spinal anterior horn motor neurons, CA regions of the hippocampus, and thalamic neurons. Astrogliosis and microgliosis. Diffuse cytoplasmic ubiquitin in cortical and spinal motor neurons and hippocampus, but rare overt inclusions. Deformed mitochondria and fission deficits. Progressive motor impairment, involving a hunched posture, muscle twitches, and reduced mobility. Impaired Rotarod performance. Complete paralysis and premature death. Postnatal growth retardation and weight loss. Transgene induced downregulation in endogenous TDP-43. Increased caspase-3 expression. Ultrastructural mitochondria abnormalities. Unknown Janssens et al., 2013 Yes
Transgene introduced into C57Bl6/C3H oocytes. Founders crossed to C57/Bl6 for a minimum of four generations. TARDBP TARDBP Q331K Full-length human TDP-43 with the Q331K mutation driven by the mouse prion protein (Prp) promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Age-dependent lower motor loss, gliosis, NMJ abnormalities and loss. No TDP-43 aggregates or cytoplasmic mislocalization. A variety of motor impairments starting around 3 months of age including tremor, abnormal hindlimb clasping, decreased Rotarod performance, and a later decrease in grip strength. Unknown Arnold et al., 2013 Yes
TDP-43Q331K KI (Line 52) C57Bl/6J Tardbp Tardp Q331K CRISPR/Cas9 mutagenesis was used to introduce a point mutation equivalent to human Q331K into the mouse Tardp gene. Tardbp: Knock-In Frontotemporal Dementia, Amyotrophic Lateral Sclerosis No TDP-43- or tau-positive inclusions. No apparent loss of upper or lower motor neurons, but 25% decrease in number of parvalbumin-positive neurons in frontal cortex. Attention deficits in a five-choice serial reaction time task, memory deficits in a novel-object-recognition task, deficits in a marble-burying task. No apparent motor impairments. Gene-expression and splicing differences, compared with wild-type mice, including upregulation of Tardp, and altered splicing of Tardp, Sort1, Mapt. Available from Jemeen Sreedharan or Robert H. Brown Jr. White et al., 2018 Yes
Elliott, WT TDP-43 (line 4) B6SJL-Tg(Prnp-TARDBP)4Jlel/J Transgene injected into B6SJLF1 oocytes. Founders crossed with CD1 mice. TARDBP Transgene expressing full-length, wild-type, human TDP-43 driven by the mouse prion protein (Prp) promoter. Transgene integrated on X chromosome. TARDBP: Transgenic Amyotrophic Lateral Sclerosis No overt neuronal loss in the brain or spinal cord.  Progressive motor impairment (variable penetrance) starting with external rotation of one hind limb followed by bilateral weakness and low muscle tone. Relatively high TDP-43 expression in skeletal muscle. Myopathy, including variable muscle fiber size and disorganization of the muscle architecture. Ubiquitin-positive inclusions in skeletal muscle cells. Status of original hybrid unknown. This model is available on a B6SJL background through The Jackson Lab: Stock# 016201; Cryopreserved Stallings et al., 2010 Yes
Julien model, Wild-type TDP-43 Transgene injected into C3H x C57Bl/6 embryos. Founders crossed with C57Bl/6. TARDBP Full-length, wild-type, human TDP-43 driven by the endogenous human promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Some denervated NMJs, gliosis (microgliosis and astrogliosis), no overt neuronal loss or loss of axons. Mostly nuclear expression of TDP-43. Age-associated cognitive and motor deficits as measured by the passive avoidance test, Barnes maze, and Rotarod. Impaired recovery following crush injury to the sciatic nerve (e.g., delayed recovery of motility, reduced axon regrowth). Normal lifespan and fertility. Not available: extinct Swarup et al., 2011 Yes
WT-TAR4/4, WT-TAR4 B6;SJL-Tg(Thy1-TARDBP)4Singh/J Transgene introduced into BL6/SJL oocytes. Founders crossed to C57BL6/J. TARDBP Transgene encodes wild-type human TARDBP, driven by the murine Thy-1 promoter. The transgene integrated at locus 6qB3 in the mouse genome and does not interrupt any known gene. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Neuronal loss in the brain and spinal cord, including anterior cortex, CA3 hippocampus, Purkinje cells, and spinal cord. Astrogliosis and microgliosis especially in the anterior cortex. Widespread diffuse ubiquitin in neurons of the brain and spinal cord, including cytoplasmic and nuclear inclusions, some co-labeling for TDP-43. Progressive motor impairment, starting at postnatal day 14, with an abnormal hindlimb reflex. Gait abnormalities, including reduced stride length and impaired performance on the accelerating Rotarod. Quick progression to muscle fasciculation’s and spasms, followed by paralysis and premature death. Elevated anxiety at a young age. Size and weight of homozygotes lag behind non-Tg and hemizygous littermates. The Jackson Lab: Stock# 012836; Cryopreserved Wils et al., 2010 Yes
Wild-type TDP-43 transgenic (line 3C), TDP-43PrP C57BL/6-Tg(Prnp-TARDBP)3cPtrc/J Transgene injected into fertilized C57BL/6 oocytes. Founders bred with B6. TARDBP Transgene expresses wild-type human TARDBP driven by the mouse prion protein (Prp) promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia No overt neuronal death, but degenerating neurites and axons, gliosis, and vacuolization of myelin. Abnormal aggregates of mitochondria present as eosinophilic aggregates in spinal motor neurons. Dendritic spine loss in the hippocampus. Homozygous mice develop body tremors and gait impairments leading to a “swimming gait” and severe motor deficits requiring euthanasia. Early reductions in body and brain weight in homozygous mice. Reduced dendritic spines in the hippocampus and lower mRNA levels of synaptic markers. The Jackson Lab: Stock# 016608; Cryopreserved Xu et al., 2010 Yes
WT-TAR6/6, TAR6/6 Transgene introduced into BL6/SJL oocytes. Founders crossed to C57BL6/J. TARDBP Transgene encodes wild-type human TARDBP, driven by the murine Thy-1.2 promoter. TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia Accumulation of transgenic and C-terminal fragments of TDP-43 in the cytoplasm, upper and lower motor neuron loss, astrogliosis, and microgliosis. Motor impairments as early as 6 weeks, reduced anxiety and disturbed nest-building behavior. Early death—average survival is 6.7 months. The CRO QPS-Austria offers research with TAR6/6 mice. Wils et al., 2010, Scherz et al., 2018 Yes
line 102 B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved Jankowsky et al., 2005 No
line 107 B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034846; Cryopreserved Jankowsky et al., 2005 No
line 885 B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034834; Cryopreserved Jankowsky et al., 2005 No
Hsiao mice, App-Swe, App-sw, APP(sw), APPSwe B6;SJL-Tg(APPSWE)2576Kha B6;SJL Mixed Background APP APP KM670/671NL (Swedish) The human APP gene (isoform 695) containing the double mutation K670N, M671L (Swedish mutation) under the control of the hamster prion protein. APP: Transgenic Alzheimer's Disease Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles or neuronal loss. Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months. Between 7 -12 weeks males become aggressive and begin to fight. Premature mortality: mortality of >20% anticipated, particularly in males. Taconic: Stock #1349 and Charles River.  The CRO PsychoGenics offers research services with this line. Hsiao et al., 1996 Yes
APPSwe-Tau, APPSwe(2576)/TauJNPL3, TAPP Tg(APPSWE)2576Kha; Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SJL, SW Mixed Background APP, MAPT APP KM670/671NL (Swedish), MAPT P301L Generated by crossing Tg2576 mice, which have the transgene for human APP (isoform 695) carrying the Swedish mutation with mice expressing human MAPT (4 repeat) with the P301L mutation. APP; MAPT: Transgenic Alzheimer's Disease Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis. Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming. Progressive hindlimb weakness. Hunched posture. Eye irritations. Some mice have the Pde6brd1 retinal degeneration mutation which can cause light sensitivity and/or blindness and may affect behavioral testing. Taconic: Stock# 2469 Lewis et al., 2001 Yes
Tg-Aβ(4-42) C57BL6 APP Transgenic encodes N-truncated human Aβ (Aβ4-42) fused to the murine thyrotropin releasing hormone signal peptide under the control of the Thy1 promoter. APP: Transgenic Alzheimer's Disease Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis. Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning. Intact vision and motor abilities. Available through Thomas Bayer. Research with this model is available from QPS Austria. Bouter et al., 2013 Yes
B6CBA-Tg(Thy1.2-hAPParc) C57BL/6-CBA APP APP E693G (Arctic) Transgenic mice with human APP (isoform 695) bearing the Arctic APP mutation (E693G). APP: Transgenic Alzheimer's Disease Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females. Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months. Available through Annica Rönnbäck Rönnbäck et al., 2011 No
Tg-Swe C57BL/6J APP APP KM670/671NL (Swedish) Transgene with human APP (isoform 695) bearing the Swedish mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months). Unknown. Available through Lars Nilsson Philipson et al., 2009, Lord et al., 2006 Yes
R1 line of ES cells APP APP KM670/671NL (Swedish) Modification of mouse APP sequence to introduce the Swedish mutation and "humanize" the murine Aβ sequence by altering three amino acids. APP: Knock-In Alzheimer's Disease Accumulation of human Aβ. Unknown. Unknown Reaume et al., 1996 No
tg ArcSwe, APP-ArcSwe C57BL/6J APP APP KM670/671NL (Swedish), APP E693G (Arctic) Transgene with human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. Tg-ArcSwe have reduced body weight compared with nontransgenic littermates. Available through Lars Nilsson Lord et al., 2006 Yes
APP(swe/ind) CRND8 Hybrid C3H/He-C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene contains human APP695 with the Swedish mutation (KM670/671/NL) and Indiana mutation (V717F) under the control of the hamster prion (PrP) gene promoter. The expression cassette includes about 90 nucleotides of the APP 5'-untranslated region adjacent to the start codon and 269 nucleotides of the 3′-untranslated region. APP: Transgenic Alzheimer's Disease Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months . Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests. Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition. Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Chishti et al., 2001 Yes
BRI2(Tg-FDD) Hybrid C3HeB/FeJ embryo; crossed to C57BL/6J ITM2B (BRI2) BRI2: Familial Danish Dementia (FDD) duplication The transgene, driven by the mouse prion promoter (Prnp), consists of the 795 form of human BRI(2) with a 10-nucleotide duplication-insertion (TTTAATTTGT). ITM2B (BRI2): Transgenic Familial Danish Dementia, Cerebral Amyloid Angiopathy, Alzheimer's Disease Widespread cerebral amyloid angiopathy (CAA) starting around 7 months. Deposition of the Danish amyloid subunit (ADan) in brain parenchyma and vessels, along with amyloid-associated gliosis and inflammation, intracellular and extracellular deposition of oligomeric ADan, and tau-positive deposits in neuropil, but no neurofibrillary tangles. Age-dependent abnormal grooming behavior. Around one year mice develop an arched back and walk with a wide-based gait and short steps. Feet clasping upon suspension of the mice by their tails. Available through Ruben Vidal Vidal et al., 2009 No
mAPP/DN-RAGE, APP/DN-RAGE C57BL/6 APP, RAGE (AGER) APP KM670/671NL (Swedish), APP V717F (Indiana) Mice expressing a form of transgenic RAGE comprising a truncated form of the receptor with intact extracellular and membrane-spanning portions, but a deleted cytosolic tail driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661--now extinct). APP: Transgenic; RAGE (AGER): Transgenic Alzheimer's Disease Diminished neuropathology compared with mice expressing mutant APP alone at both 3–4 and 14–18 months of age. Preservation of spatial learning and memory compared with Tg-mAPP/RAGE animals. No abnormalities with respect to reproductive fitness, development, basic neurological functioning, or longevity. Available through Shirley ShiDu Yan Arancio et al., 2004 No
APP/RAGE C57BL/6 APP, RAGE (AGER) APP KM670/671NL (Swedish), APP V717F (Indiana) Mice expressing human wild-type RAGE driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661-now extinct) APP: Transgenic; RAGE (AGER): Transgenic Alzheimer's Disease Increased activation of microglia and astrocytes compared to mice expressing mutant APP alone. Abnormalities in spatial learning and memory at 3-4 months of age, whereas deficits occur later in mice expressing mutant APP alone and are less severe. Available through Shirley ShiDu Yan Arancio et al., 2004 No
APP-Swedish,Dutch,Iowa, APPSwDI C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6 APP APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) Transgenic mice with 2.1 kb of the human APP gene (isoform 770) with the Swedish (K670N/M671L), Dutch (E693Q) and Iowa (D694N) mutations under the control of the mouse Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months. Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination. The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live Davis et al., 2004 Yes
mThy1-α-synuclein, mThy-1 tg, Tg(Thy1-SNCA)61Ema B6;DBA-Tg(Thy1-SNCA)61Ema (C57BL/6 x DBA/2)F1 (strain of origin) SNCA This transgenic mouse expresses human wild-type α-synuclein under the control of the mouse Thy1 promoter (Rockenstein et al., 2002). The transgene is inserted in the X chromosome. SNCA: Transgenic Parkinson's Disease Available through Eliezer Masliah, Robert Rissman for academic research; others please contact the Office of Innovation and Commercialization at the University of California, San Diego. Rockenstein et al., 2002 Yes
Tau22 C57BL6/CBA; backcrossed to C57BL6 MAPT MAPT G272V, MAPT P301S Transgene containing the cDNA of the 412 amino acid isoform of human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2 promotor. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis. Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission. Available through Luc Buée Schindowski et al., 2006 Yes
Thy-1 mutated human tau, TAU 441, hTAU441, TAU441 V337M R406W C57Bl/6xDBA MAPT MAPT V337M (Seattle), MAPT R406W Transgene consists of human MAPT Tau441 (2N/4R) with mutations V337M and R406W under control of the Thy1 promoter. MAPT: Transgenic Alzheimer's Disease Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months. Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test). Olfactory deficits. The CRO QPS-Austria offers research services with this line. Flunkert et al., 2013 Yes
Thy-1 PS1.M146V Transgene injected into fertilized oocytes from pure C57BL/6 mice. PSEN1 PSEN1 M146V Transgene encoding human PSEN1 carrying the M146V mutation. Transgene is driven by the murine Thy-1 promoter. PSEN1: Transgenic Alzheimer's Disease No plaques. Unknown. Unknown Howlett et al., 2004 No
BAC-TREM2 FVB/NJ TREM2 The BAC (RP11-237K15) transgene contains the TREM2 coding region and surrounding genomic regions (>50 kb on each side) with conserved gene regulatory elements. Key coding exons were deleted from other TREM-like genes contained in the BAC, to prevent their expression. Transgenic mice were generated and maintained on the FVB/NJ background. TREM2: Transgenic Alzheimer's Disease No obvious neuropathology is observed at 4, 7 and 11 months of age. Normal contextual fear conditioning at 10 months of age. Normal LTP at 10 months of age. Available through X. William Yang. Lee et al., 2018 Yes
BAC-TREM2 X 5xFAD TREM2-BAC: FVB/NJ; 5xFAD: C57BL/6 X SJL TREM2, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V TREM2-BAC mice were crossed with 5xFAD mice. TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD. 5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired. TREM2-BAC: Available through X. William Yang. 5xFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live Lee et al., 2018 Yes
B6(C3)-Trem2tm1c(EUCOMM)Wtsi/AdiujJ B6(C3) Trem2 Targeted insertion of LoxP sites flanking exons 2 and 3 of the mouse Trem2 gene. Trem2: Knock-In Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease No data. No data. The Jackson Lab: Stock# 029853; Live The Jackson Laboratory No
CV+mTrem2−/−5XFAD C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5xFAD mice. Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques surrounded by activated microglia. No data. Neurodegeneration-associated microglial activation markers elevated, compared with 5XFAD lacking TREM2. TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Song et al., 2018 Yes
R47H+mTrem2−/−5XFAD C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 TREM2 R47H, APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V BAC-transgenic mice carrying the human TREM2 (R47H variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5XFAD mice. Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. No data. TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Song et al., 2018 Yes
Trem2-/- (Colonna) C57BL/6 -TREM2tm1cln C57BL/6 Trem2 Inactivation of the mouse Trem2 gene by targeted deletion of exons 3 and 4 Trem2: Knock-Out Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease Microglial number remains constant and microglial size decreases with age in the corpus callosum of Trem2 KO mice, while microglial number increases and microglial size remains stable in wild-type mice. No cognitive/behaviorial deficits observed. Osteopenic. Impaired microglial response to experimental demyelination, middle cerebral artery occlusion, and facial nerve axotomy. Available through Marco Colonna Turnbull et al., 2006 Yes
Trem2-/-5XFAD, mTrem2-/-5XFAD  C57BL/6 -TREM2tm1cln; B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmja C57BL/6 Trem2, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5XFAD mice were crossed with Trem2 KO mice. TREM2 KO: Targeted deletion of exons 3 and 4 of mouse Trem2. 5XFAD express two transgenes: 1) human APP with the Swedish, Florida and London mutations, containing the 5' untranslated region and driven by the mouse Thy1 promoter and 2) human PSEN1 with the M146L and L286V mutations driven by the mouse Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes. No data. Trem2 KO: available through Marco Colonna. 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Wang et al., 2015 Yes
Trem2-/-PS19 C57BL/6 -TREM2tm1cln; B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J C57BL/6 Trem2, MAPT MAPT P301S Trem2 KO (Colonna) mice were crossed with PS19 mice. TREM2 KO: Inactivation of the mouse Trem2 gene was achieved by targeted deletion of exons 3 and 4. PS19: express human MAPT (1N4R) with the P301S mutation, driven by the mouse prion protein (Prnp) promoter. Trem2: Knock-Out; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Microgliosis, astrogliosis, and brain atrophy in Trem2-/-PS19 mice are greatly attenuated compared with Trem2+/+PS19 animals. No data. Trem2 KO: available through Marco Colonna. PS19: The Jackson Lab: Stock# 008169; Live Leyns et al., 2017 Yes
C57BL/6J-Trem2em2Adiuj/J C57BL/6J Trem2 Trem2 expression was ablated using CRISPR/Cas9. Non-homologous end joining resulted in a 175-bp deletion that introduced a stop codon at amino acid 17. Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease No data.. No data. The Jackson Lab: Stock# 027197; Live The Jackson Laboratory Yes
Trem2 −/− (KOMP) Trem2tm1(KOMP)Vlcg C57BL/6N Trem2 The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ -p(A)-loxP-hUbCpro-neor-p(A)-loxP). Trem2: Knock-Out Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease No data. At six months, mice perform normally in the open-field test, elevated plus maze, three-chamber social-interaction test, and contextual and cued fear-conditioning test. Trem2−/− microglia show a muted response to excitotoxicity in vivo, and decreased proliferation and increased apoptosis in vitro. Overexpression of Treml1 is driven by an ectopic Ubiquitin C promoter in the selection cassette. UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm Kang et al., 2018 Yes
APPPS1;Trem2-/- TREM2tm1(KOMP)Vlcg; B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6 Trem2, APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 L166P Trem2-/-: The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ-p(A)-loxP-hUbCpro-neor-p(A)-LoxP). APPPS1: Mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1. No data. APPPS1 available through Mathias Jucker; Trem2 KO available through UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm Jay et al., 2015, Jay et al., 2017 Yes
hTau;Trem2−/− TREM2tm1(KOMP)Vlcg; B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J C57BL/6 Mapt, MAPT, Trem2 Htau mice were bred to Trem2−/− mice (Trem2tm1(KOMP)Vlcg) to generate hTau;Trem2−/− and htau/Trem2+/+ mice. These mice were backcrossed for four generations, and maintained on a C57BL/6 background. Mapt: Knock-Out; MAPT: Transgenic; Trem2: Knock-Out Nasu-Hakola Disease, Alzheimer's Disease, Frontotemporal Dementia Tau phosphorylation and aggregation in the cortex are enhanced in htau mice lacking TREM2, but reactive microglia are smaller and their processes have fewer branches. No data. Levels of stress-related protein kinases are elevated in the cortices and hippocampi of hTau;Trem2−/− compared with htau;Trem2+/+ mice. htau: The Jackson Lab: Stock# 005491, live; the CRO QPS-Austria offers research with this line. Trem2 KO: UC Davis KOMP Repository, Project VG10093, cryorecovery or sperm. Bemiller et al., 2017 Yes
R47H ki Trem2em2 Bwef C57BL/6N Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce an R47H point mutation (arginine CGC > histidine CAC) and three silent mutations (glycine: GGG > GGT; arginine: AGA > CGA; lysine: AAG > AAA) into the mouse Trem2 gene. The silent mutations were added to aid in genotyping and increase the efficiency of gene editing. Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. R47H KI mice exhibit a gene-dose-dependent reduction in expression of Trem2, due to aberrant splicing of the mutant allele. Available through Christian Haass. Xiang et al., 2018 Yes
MODEL-AD R47H C57BL/6J-Trem2em1Adiuj/J C57BL/6J Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce a point mutation into the endogenous mouse Trem2 gene, resulting in an arginine-to-histidine substitution at amino acid 47 (R47H). Trem2: Knock-In Alzheimer's Disease Unknown. At 2 and 12 months of age, R47H KI mice perform similarly to wild-type mice in tests of locomotor activity, motor coordination, and working memory. Levels of Trem2 mRNA (measured in brain) and protein (measured in bone-marrow-derived macrophages) are decreased in homozygous R47H KI mice compared with wild type mice. The Jackson Lab:Stock# 027918; Live The Jackson Laboratory Yes
Trem2+/R47H C57BL6/J Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. Trem2: Knock-In Alzheimer's Disease No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age. Unknown. Approximate 40 percent decrease in levels of Trem2 mRNA in cortices of Trem2+/R47H mice compared with Trem2+/+ mice. Available through Gary Landreth or Bruce Lamb. Cheng-Hathaway et al., 2018 Yes
APPPS1-21;Trem2+/R47H C57BL6/J Trem2, APP, PSEN1 TREM2 R47H, APP KM670/671NL (Swedish), PSEN1 L166P To create Trem2+/R47H mice, CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. APPPS1-21 mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2. Unknown. Levels of Trem2 transcripts were reduced in APPPS1-21;Trem2+/R47H compared with APPPS1-21;Trem2+/+ and were similar to those in APPPS1-21 mice haploinsufficient for Trem2. Trem2+/R47H available through Gary Landreth or Bruce Lamb; APPPS1-21 available through Mathias Jucker. Cheng-Hathaway et al., 2018 Yes
APOE4/Trem2*R47H B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J B6(SJL) APOE, Trem2 TREM2 R47H This double-mutant line was generated by crossing a line carrying a humanized APOE4 gene (Jackson Lab Stock# 027894) to a line carrying an R47H point mutation knocked into the mouse Trem2 gene (Jackson Lab Stock # 027918). APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease No data. No data. The Jackson Lab:Stock# 028709; Live The Jackson Laboratory Yes
Trem2 p.T66M Trem2em1Bwef Mixed DBA/2J, FVB/ N, C57BL/6J Trem2 TREM2 T66M A CA>TG substitution was introduced into the murine Trem2 gene using CRISPR/Cas9 genome editing, resulting in a threonine-to-methionine substitution at amino acid 66.. Trem2: Knock-In Frontotemporal Dementia Age-related microglial activation seen in wild-type mice is absent in homozygotes. No data. Reduced cerebral blood flow and reduced cerebral glucose metabolism in homozygotes. Bone marrow-derived macrophages from heterozygous and homozygous Trem2 T66M mice show reduced proliferation, survival, and phagocytosis. Available through Christian Haass Kleinberger et al., 2017 Yes
C57BL/6J-Trem2em3Adiuj/J C57BL/6J Trem2 TREM2 Y38C CRISPR/Cas9 was used to introduce a point mutation into the endogenous mouse Trem2 gene, resulting in a tyrosine-to-cysteine amino acid substitution at amino acid 38 (Y38C). Trem2: Knock-In Frontotemporal Dementia No data. No data. The Jackson Lab: Stock# 029725; Cryopreserved Yes
Segmentally trisomic Ts(1716)65Dn, Down Syndrome-segmental trisomy 16 B6EiC3Sn a/A-Ts(1716)65Dn/J DBA/2J Cesium irradiation produced a reciprocal translocation of chromosomes 16 and 17, creating a freely segregating, supernumerary chromosome Mmu1716 (1716). Other Alzheimer's Disease, Down's Syndrome Brain is grossly normal. Age-dependent cholinergic neurodegeneration and reduced NGF in the basal forebrain. Age-related elevation of APP and Aβ in the hippocampus but no β-amyloid pathology. Early developmental delay. Deficits in behavioral and cognitive tasks including spatial learning and memory deficits as assessed by the Morris water maze and the radial arm maze. Developmental delay in sensorimotor milestones. Locomotor hyperactivity. Lack of behavioral inhibition. Stereotypic behavior. Females are smaller, and produce fewer, smaller litters. Males are effectively sterile with hypospermia. The Jackson Lab: Stock# 001924; Live. The CRO PsychoGenics offers research services with this line. Davisson et al., 1990 No
WSB.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How WSB/EiJ APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with WSB/EiJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in cortex and hippocampal area CA1 in females. Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in females (data from males is not available, as wild-type males are unable to perform this test). Available from The Jackson Laboratory, Stock #25970. Onos et al., 2019 Yes
Rat Models (14)
AgenT Wistar APP, PSEN1 APP KM670/671NL (Swedish), APP V717I (London), PSEN1 M146L (A>C) Adeno-associated viral vectors separately encoding human APP with the Swedish and London mutations and human PSEN1 with the M146L mutation were injected bilaterally into the hippocampi of young adult (8-week-old) rats. APP: Virus; PSEN1: Virus Alzheimer's Disease Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection. Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field. At 8 months post-injection, long-term potentiation was impaired in hippocampal slices obtained from AAV-AD rats, compared with controls, but the groups did not differ with regards to long-term depression. Viral vectors are available through AgenT SAS under collaboration or partnership agreements. Audrain et al., 2017 Yes
F344-Tg(APP)21Besey Fischer 344 APP APP KM670/671NL (Swedish), APP V717F (Indiana) A lentiviral vector carrying a human APP695 transgene was injected into Fischer 344 zygotes. This transgene contains the Swedish and Indiana mutations and is driven by the ubiquitin-C promoter. APP: Transgenic Alzheimer's Disease No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males. Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age. Available from the Rat Resource & Research Center, Stock# 00636; cryorecovery, sperm Agca et al., 2008 Yes
Fischer 344 APP, PSEN1 APP KM670/671NL (Swedish), APP V717F (Indiana), PSEN1 L166P APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age. Deficits in Barnes maze by 10 months of age. Agca et al., 2016, Klakotskaia et al., 2018 Yes
DJ-1 knockout rat LEH-Park7tm1sage Long Evans Hooded PARK7 (DJ1) Disruption of the DJ-1 gene by zinc finger nuclease (ZFN) technology. ZFNs were engineered to bind to a recognition sequence in exon 5 of PARK7 and cleave DNA. PARK7 (DJ1): Knock-Out Parkinson's Disease Age-related decrease in dopaminergic neurons in the substantia nigra and locus coeruleus; approximately 50 percent reduction by 8 months. Striatal dopamine and serotonin levels elevated 2-3fold over wild-type levels. No change was found in TH-immunoreactivity in the ventral tegmental area or striatum. Abnormalities in gait and strength, vocalizations, and tongue movements. Dragging hind limbs in some animals as early as 4-6 weeks. By 4 months, abnormal paw positioning and a shorter stride. In males, impaired licking, longer and more frequent ultrasonic vocalizations, and accelerated decrease in average call intensity with age. No increase in mortality up to 8 months of age. Available through Horizon Discovery (formerly Sage Labs), Cat #TGRL4830; Live. Dave et al., 2014 Yes
Line 10681, hBAC G2019S-LRRK2, LRRK2 G2019S rat NTac:SD-Tg(LRRK2*G2019S)571CJLi Sprague-Dawley LRRK2 LRRK2 G2019S BAC construct carrying the human gene Lrrk2 with the G2019S mutation. LRRK2: Transgenic Parkinson's Disease No overt neurodegeneration out to 12 months of age. Elongated dopaminergic neurons. Elevated oxidative and nitrosative stress. No evidence of gliosis. No α-synuclein inclusions until challenged with exogenous α-synuclein. No change in dopamine levels. Mild abnormalities in motor behavior. Slightly more postural instability at eight months of age (but not at four and 12 months). Slightly more rearing events at 12 months, but not at younger ages. Available through Taconic, Cat# 10681, Live. West et al., 2014 Yes
Lrrk2 knockout rat LEH-Lrrk2tm1sage Long Evans Hooded LRRK2 Zinc finger nuclease (ZFN) technology was used to generate a deletion of 10 base pairs in exon 30 of the rat Lrrk2 gene. This resulted in a frameshift and a premature stop codon in the same exon. LRRK2: Knock-Out Parkinson's Disease Not observed. Protection against dopaminergic cell loss under conditions involving LPS or α-synuclein overexpression in the substantia nigra. One assessment of Rotarod performance revealed no impairment at 12 months. Abnormalities in peripheral organs, including the kidney, liver, and lung. Available through Horizon (formerly Sage Labs), Cat #TGRL4620, Live. Baptista et al., 2013, Ness et al., 2013 Yes
HsdBrl:WH Wistar APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene contains entire coding region of human APP751 with the Swedish and Indiana mutations and approximately 900 bp of 3' non-translated sequence, driven by the murine Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Hemizygotes: intraneuronal Aβ in hippocampus and cortex by one week, but no plaques even at advanced ages. Homozygotes: intraneuronal Aβ in hippocampus and cortex by one week; amyloid plaques in hippocampus beginning at 6 months, in cortex beginning at 13 months. Cognitive deficits are apparent by three months of age in both hemizygous and homozygous transgenic rats. Resting-state fMRI showed disrupted cingulate network connectivity by 9 to11 months; FDG-PET showed hypometabolism by 16 to 19 months (homozygotes). Breeding pairs available via a royalty agreement with McGill University; contact Adriana Ducatenzeiler. Leon et al., 2010 Yes
Park2 KO, Parkin knockout rat LEH-Park2TM1sage Long Evans Hooded PRKN (parkin) The rat Park2 gene was disrupted using zinc finger nuclease (ZFN) technology. The targeted ZFN created a DNA strand break in exon 4 of Park2. Repair of this break created a deletion of five base pairs, leading to a frame shift and the creation of a premature stop codon. PRKN (parkin): Knock-Out Parkinson's Disease No significant changes in dopaminergic neurons in the substantia nigra nor striatal dopamine levels, but alterations in dopaminergic signaling were detected at an early age, as were disruptions in mitochondrial function and protein expression in striatal synapses. No increase in α-synuclein protein in the striatum or other brain regions. No behavioral deficits detected at 4, 6, and 8 months of age. However, at 2 months, male KO rats made fewer small stereotypic movements, such as scratching and grooming, than wild-type controls. Available through Horizon Discovery (formerly Sage Labs); TGRL4760; Live. Dave et al., 2014 Yes
Pink1 knockout rat, PARK6 KO rat LEH-Pink1tm1Sage-/- Long Evans Hooded PINK1 The rat Pink1 gene was disrupted using zinc finger nuclease (ZFN) technology. The ZFNs were engineered to bind to a recognition site in exon 4 of Pink1 and cleave the DNA. When the resulting double strand break was repaired, a deletion of 26 base pairs was created. This deletion lead to a frameshift and the creation of a premature stop codon. PINK1: Knock-Out Parkinson's Disease Age-related decrease in dopaminergic neurons in the substantia nigra; greater than 50 percent reduction at eight months. Alterations in striatal dopamine and serotonin levels. Progressive increase in α-synuclein aggregates in periaqueductal gray, substantia nigra pars compacta, locus coeruleus, nucleus ambiguus, cortex, thalamus, and striatum. Alterations in cortical and striatal mitochondria. Abnormalities in gait, coordination, and strength. As early as 5 weeks of age, KOs had increased foot slips on the tapered balance beam, at 7 weeks they showed hind limb fatigue, which progressed to hind limb dragging, and by 2 months they exhibited alterations in oromotor behaviors. Heavier than wild-type rats at 4, 6, and 8 months of age. No increase in mortality. Available through Horizon Discovery (formerly Sage Labs), Cat# TGRL4690; Live. Dave et al., 2014 Yes
SHR MAPT SHR24 rats express a gene encoding amino acids 151-274 and 306-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R). MAPT: Transgenic Alzheimer's Disease Neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem, beginning at 9 to 10 months. No neuron loss was observed in the hippocampus or cortex. SHR24 rats exhibit age-dependent impairments in several neurobehavioral tests; hind-limb clasping during the tail-hang test is one of the earliest abnormalities to appear, evident by 3.5 months of age. SHR24 rats have a shorter lifespan (approximately 14 months) than wild-type SHR rats (22-24 months). Unknown. Filipcik et al., 2012, Valachova et al., 2018 Yes
SHR MAPT SHR318 rats express a gene encoding amino acids 151-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R). MAPT: Transgenic Alzheimer's Disease Neurofibrillary tangles first appear at 9 months and are particularly prominent in the brainstem and spinal cord. Axonal degeneration is observed in the brainstem and spinal cord of 10- to 12-month animals. At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze. Reflexes and sensorimotor coordination are impaired at 7 months. SHR72 rats have a shorter lifespan (approximately 10–12 months) than wild-type SHR rats (22–24 months). No longer available. Zilka et al., 2006, Hrnkova et al., 2007 Yes
SHR MAPT SHR72 rats express a gene encoding amino acids 151-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R). MAPT: Transgenic Alzheimer's Disease Neurofibrillary tangles, demonstrated by Gallyas silver stain, were found the brainstems and spinal cords of terminal stage (7- to 8-month old) animals. Chromatolytic neurons and damaged axons were also observed at this stage. Sensorimotor deficits and loss of muscle strength are apparent at 3 months. This stage lasted about three months, and then rats experienced a rapid, dramatic decline in neurological function, succumbing within several days. SHR72 rats have a shorter lifespan (approximately 7-8 months) than wild-type SHR rats (22-24 months). Unknown. Koson et al., 2008 Yes
α-synuclein (E46K) rat, founder line 70, Human α-synuclein E46K rat, E46K aSyn Rat, Alpha-synuclein E46K Rat (BAC Tg) NTac:SD-Tg(SNCA*E46K)70CJLi Sprague-Dawley SNCA SNCA E46K A bacterial artificial chromosome (BAC) was used to introduce human α-synuclein with the E46K mutation. SNCA: Transgenic Parkinson's Disease No overt neuronal loss. Accumulation of mutant α-synuclein in the brain, in the form of diffuse staining and intracellular aggregates. Aggregates were largely restricted to dopaminergic neurons of the substantia nigra and ventral tegmental area. Elevated nitrotyrosine in dopaminergic neurons. No overt behavioral changes until challenged with low-dose rotenone, upon which the rats exhibit bradykinesia, postural instability, and rigidity. Viable and fertile. Available through Taconic Cat #10679; Cryopreserved. Cannon et al., 2013 Yes
Fischer 344 APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 TgF344-AD rats express human APP with the Swedish mutation and human PSEN1 with the Δ exon 9 mutation. Both transgenes are driven by the mouse prion promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, microgliosis, and astrogliosis by 6 months. Neurofibrillary tangle-like structures at 16 months. Approximate 40 percent loss of neurons in hippocampus and cortex by 16 months. Earliest reported deficits are in reversal learning in the Morris water maze, apparent by 6 months. Available through Terrence Town. Cohen et al., 2013 Yes

202 Visualizations

AD-related Research Models

Phenotypes Examined

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.

3xTg

Observed
  1. X
    Plaques at 26

    Extracellular Aβ deposits by 6 months in the frontal cortex, predominantly layers 4 and 5 and progress with age (Oddo et al., 2003).

  2. X
    Tangles at 52

    By 12 months extensive tau immunoreactivity in CA1 neurons of the hippocampus, particularly pyramidal neurons, later in the cortex. No tau pathology at 6 months (Oddo et al., 2003).

  3. X
    Gliosis at 30

    Increased density of GFAP immunoreactive astrocytes and IBA-1 immunoreactive microglia compared with wild-type mice at 7 months (Caruso et al., 2013). Development of gliosis may occur earlier.

  4. X
    Changes in LTP/LTD at 26

    By 6 months decreased LTP compared with wild type controls. Impairment in basal synaptic transmission. No change at 1 month of age (Oddo et al., 2003).

  5. X
    Cognitive Impairment at 17

    Cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala, but plaques and tangles are not yet apparent (Billings et al., 2005).

Absent
No Data
  • Neuronal Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1, MAPT APP KM670/671NL (Swedish), MAPT P301L, PSEN1 M146V APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease

Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles.

Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task.

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5xFAD (B6SJL)

Observed
  1. X
    Plaques at 8

    Extracellular amyloid deposition begins around 2 months, first in the subiculum and layer V of the cortex. Aβ42 also accumulates intraneuronally in an aggregated form within the soma and neurites starting at 1.5 months.

  2. X
    Neuronal Loss at 24

    Neuron loss in cortical layer V and subiculum.

  3. X
    Gliosis at 8

    Gliosis begins at 2 months.

  4. X
    Synaptic Loss at 16

    Levels of the presynaptic marker synaptophysin begin to decline by 4 months; levels of syntaxin, another presynaptic marker, and PSD-95, a postsynaptic marker, decline by 9 months

  5. X
    Changes in LTP/LTD at 24

    Basal synaptic transmission and LTP in hippocampal area CA1 begin to deteriorate between 4 and 6 months

  6. X
    Cognitive Impairment at 18

    Impaired spatial working memory in the Y-maze test and impaired remote memory stabilization in a contextual-fear-conditioning test by 4 to 5 months of age.

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles.

Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype.

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5xFAD (C57BL6)

Observed
  1. X
    Plaques at 8

    Amyloid plaques observed in hippocampus, cortex, thalamus, and spinal cord.

  2. X
    Neuronal Loss at 52

    Approximate 40 percent loss of layer V pyramidal neurons at one year.

  3. X
    Gliosis at 8

    Microgliosis and astrogliosis are associated with amyloid plaques; microgliosis is associated with vascular damage.

  4. X
    Synaptic Loss at 24

    Spine density was reduced in pyramidal neurons in somatosensory and prefrontal cortices, but not in the hippocampi, of 5xFAD mice crossed with mice expressing yellow fluorescent protein (YFP mice), compared with mice expressing YFP alone.

  5. X
    Changes in LTP/LTD at 8

    While spike-timing-dependent long-term potentiation was induced in layer V neurons from wild-type mice, the same stimulation protocol induced long-term depression in neurons from 5xFAD mice.

  6. X
    Cognitive Impairment at 24

    Impairments of spatial working memory and reduced anxiety emerge between 3 and 6 months and worsen with age.

Absent
No Data
  • Tangles at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer V.

Age-dependent memory deficits, motor phenotype, and reduced anxiety.

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A7 APP transgenic

Observed
  1. X
    Plaques at 39

    These mice develop progressive amyloid deposition in the cerebral cortex by 9-12 months. By 21 months of age amyloid pathology is extensive.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP T714I (Austrian) APP: Transgenic Alzheimer's Disease

Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months.

Unknown.

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AAV-AD

Observed
  1. X
    Plaques at 128

    Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection.

  2. X
    Changes in LTP/LTD at 40

    Deficits in LTP as Schaffer collateral-CA1 synapse at 10 months (8 months post-injection).  LTD similar to controls.

  3. X
    Cognitive Impairment at 40

    AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training.

Absent
  • Gliosis at

    No astrogliosis observed up to 30 months post-injection.

No Data
  • Tangles at

    Immunostaining with monoclonal antibodies AT8 and AT100 suggests the presence of (pre)tangle-like structures 30 months post-injection.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP V717I (London), PSEN1 M146L (A>C) APP: Virus; PSEN1: Virus Alzheimer's Disease

Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection.

Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field.

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AAV-GFP-(GA)50

Observed
  1. X
    Motor Impairment at 24

    Deficits in tail-suspension and rotarod tests, seen at 6 months.

  2. X
    Cortical Neuron Loss at 24

    At 6 months, neuron loss observed in cortex, including layer V of motor cortex.

  3. X
    Cytoplasmic Inclusions at 5

    Neuronal poly(GA)- and ubiquitin-positive inclusions already present at 4-6 weeks; rare TDP-43-positive inclusions.

  4. X
    Body Weight at 24

    Decreased body weight in males, but not females, seen at 6 months.

  5. X
    Gliosis at 24

    Astrogliosis, but not microgliosis, in cortex and hippocampus, seen at 6 months.

Absent
No Data
  • Lower Motor Neuron Loss at

    No data.

  • NMJ Abnormalities at

    No data.

  • Muscle Atrophy at

    No data.

  • Premature Death at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Poly(GA)- and ubiquitin-positive inclusions in neurons are primarily cytoplasmic and also co-localize with HR23A and HR23B proteins and the nuclear pore complex proteins RanGAP1 and Pom121. Neuron loss and astrogliosis in cortex and hippocampus.

Motor deficits, impaired coordination, hyperactivity, increased anxiety, and deficits in contextual and cued fear conditioning.

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AAV-GFP–(GR)100

Observed
  1. X
    Motor Impairment at 12

    Progressive motor deficits, seen in open-field, rotarod, rod-walk, and wire-hang tests.

  2. X
    Cortical Neuron Loss at 6

    Fewer cortical neurons than controls, observed as early as 6 weeks of age.

  3. X
    Cytoplasmic Inclusions at 24

    Very rare TDP-43 inclusions, observed at 6 months.

  4. X
    Gliosis at 6

    Astrogliosis and microgliosis in cortex and hippocampus, observed at 6 weeks.

Absent
  • Lower Motor Neuron Loss at

    Not observed up to 6 months of age.

  • Body Weight at

    Normal at 6 months of age.

No Data
  • NMJ Abnormalities at

    No data.

  • Muscle Atrophy at

    No data.

  • Premature Death at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Progressive neuron loss in cortex and hippocampus, gliosis. Lacks poly(GR) inclusions. Rare TDP-43 inclusions.

Progressive motor deficits and age-dependent cognitive impairment.

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Abca7*A1527G/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Abca7, APOE, Trem2 TREM2 R47H Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Abca7 KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Abca7, APOE, Trem2 TREM2 R47H Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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ADanPP

Observed
  1. X
    Plaques at 9

    Vascular amyloid deposits and punctate parenchymal aggregates first occur in the hippocampus and increase with age, spreading throughout the brain, including the cortex, amygdala, thalamus, and brainstem in hemizygous mice.

  2. X
    Gliosis at 17

    Astrogliosis and microgliosis increase with age and increasing ADan-amyloid deposition.

  3. X
    Cognitive Impairment at 78

    The only ages tested were 6 months and 18-20 months. Mice 18-20 months of age exhibited both motor and spatial learning defects in the Morris water maze, and increased anxiety in the open field test. No impairments were observed in 6 month-old mice.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
ITM2B (BRI2) BRI2: Familial Danish Dementia (FDD) duplication ITM2B (BRI2): Transgenic Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy

ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present.

Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype.

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AD-BXD

Observed
  1. X
    Plaques at 24

    Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, the earliest age examined. The extent of plaque deposition is strain-dependent.

  2. X
    Gliosis at 25

    Strain-dependent gliosis by 6 months. 

  3. X
    Cognitive Impairment at 60

    In the AD-BXD population as a whole, transgenic mice performed similarly to non-transgenic littermates in a contextual fear-conditioning test at 6 months, but were impaired at 14 months. The age of onset and severity of impairment are strain-dependent.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent.

Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent.

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APOE2 Knock-In, floxed (CureAlz)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE2 Knock-In (JAX)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE2 Targeted Replacement

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE3 Knock-In, floxed (CureAlz)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE3 Knock-In (JAX)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

No data.

No data.

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APOE3 Knock-In (Lamb)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury

Unknown.

Unknown.

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APOE3 Targeted Replacement

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE4 Knock-In, floxed (CureAlz)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE4 Knock-In (JAX)

Observed
Absent
  • Cognitive Impairment at

    At 2 and 12 months of age, APOE4 KI mice perform similarly to wild-type mice in tests of locomotor activity, motor coordination, and working memory.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

No data.

No data.

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APP21

Observed
  1. X
    Neuronal Loss at 76

    Necrotic neurons in hippocampus and cortex of female rats.

  2. X
    Gliosis at 64

    Activated (MHCII-positive) microglia present in white matter tracts at 15 months.

  3. X
    Cognitive Impairment at 12

    Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

Absent
  • Plaques at

    Do not spontaneously develop amyloid pathology, but can serve as hosts for exogenously seeded amyloid deposits.

No Data
  • Tangles at

    “Flame-shaped” profiles in hippocampal neurons of 18- to 19-month-old female rats revealed by hematoxylin-and-eosin-staining.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males.

Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

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APP23

Observed
  1. X
    Plaques at 26

    Congophillic, dense-core amyloid plaques first appear at 6 months, and increase in size and number with age. Amyloid plaques can occupy more than 25% of the neocortex and hippocampus in 24 month-old mice (Sturchler-Pierrat et al., 1997; Calhoun et al., 1998).   

  2. X
    Neuronal Loss at 61

    Neuronal loss (14-28%) has been reported in the CA1 region of the hippocampus in 14-18 month old mice (Calhoun et al., 1998).     

  3. X
    Gliosis at 26

    Activated microglia in close proximity to dense amyloid plaques (Stalder et al., 1999). Upregulation of neuroinflammatory markers and activation of astrocytes and macrophages. Age-associated increase in components of the complement system, namely C1q and C3, at later ages (9 and 18 months, respectively) (Reichwald et al., 2009). 

  4. X
    Cognitive Impairment at 13

    Spatial memory defects in Morris Water maze at 3 months and progresses with age (Van dam et al., 2003; Kelly et al., 2003).

Absent
  • Tangles at

    Dystrophic neurites containing hyperphopshorylated tau surounds Aβ plaques, but no neurofibrillary tangles are observed (Sturchler-Pierrat et al., 1997).

  • Synaptic Loss at

    Neocortical synapses were examined in mice as old as 24 months of age; no evidence of alterations in the number of synapses or levels of synaptophysin were observed (Boncristiano et al., 2005).

  • Changes in LTP/LTD at

    LTP in the hippocampus and prefrontal cortex is normal at all ages studied: 3, 6, 9, 12, 18 and 24 months (Roder at al., 2003).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages.

Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages.

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APP23 x PS1-R278I

Observed
  1. X
    Plaques at 26

    By 6 months of age amyloid plaques accumulate in the cortex and hippocampus. A high percentage of plaques are thioflavin-S –positive cored plaques.

  2. X
    Gliosis at 39

    Astrocytosis in the vicinity of plaques in the hippocampus and cortex by 9 months.

  3. X
    Cognitive Impairment at 13

    Short-term memory deficits are apparent by 3 to 4 months as measured by the Y maze.

Absent
  • Tangles at

    Not observed.

No Data
  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 PSEN1 R278I APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease

Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques.

Short-term memory deficits apparent by 3-4 months as measured by the Y maze.

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APP751SL/PS1 KI

Observed
  1. X
    Plaques at 11

    Aβ deposition at 2.5 months compared to 6 months in APPSL mice. At 6 months, numerous compact Aβ deposits in the cortex, hippocampus, and thalamus, whereas in age-matched APPSL mice only very few deposits restricted mainly to the subiculum and deeper cortical layers. At 10 months, deposits increased in distribution, density, and size in both models (Casas et al., 2004).

  2. X
    Neuronal Loss at 23

    Some cell loss detectable as early as 6 months in female mice. At 10 months extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer. SNeuronal loss also occurs in the frontal cortex and cholinergic system (Casas et al., 2004; Christensen et al., 2008; Christensen et al., 2010).

  3. X
    Gliosis at 11

    Astrogliosis occurs in parallel with Aβ deposition, starting around 2.5 months, and in proximity to Aβ-positive neurons (Wirths et al., 2010).

  4. X
    Synaptic Loss at 24

    At 6 months, levels of pre- and post-synaptic markers are reduced (Breyhan et al., 2009).

  5. X
    Changes in LTP/LTD at 28

    At 6 months there is a large reduction of long-term potentiation and disrupted paired pulse facilitation. No deficit at 4 months (Breyhan et al., 2009).

  6. X
    Cognitive Impairment at 27

    Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates (Wirths et al., 2008).

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease

Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons.

Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates.

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APPDutch

Observed
  1. X
    Gliosis at 126

    Microgliosis develops after the onset of CAA pathology and is prominent in areas adjacent to amyloid-laden vessels. There is also widespread activation of astrocytes in neocortical regions affected by CAA. These changes have been reported at 29 months of age, although the actual onset of gliosis may occur earlier than has been examined.

Absent
  • Plaques at

    No plaques are observed, but CAA develops at 22-24 months.

  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP E693Q (Dutch) APP: Transgenic Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease

Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed. 

Unknown.

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APP E693Δ-Tg (Osaka)

Observed
  1. X
    Neuronal Loss at 104

    Neuronal loss, as measured by NeuN staining, was observed in the CA3 region of the hippocampus at 24 months of age. Neuronal loss was not detected in the cerebral cortex at this time.

  2. X
    Gliosis at 52

    At 12 months of age, microgliosis is seen in transgenic mice, as measured by the presence of Iba-1 staining in the hippocampus and cortex. Astrocytosis, as measured by GFAP-reactivity, increased starting around 18 months of age in these regions.

  3. X
    Synaptic Loss at 34

    Starting around eight months of age, transgenic mice exhibit a decrease in synaptic density in the CA3 region of the hippocampus as measured by synaptophysin staining.

  4. X
    Changes in LTP/LTD at 35

    By eight months of age, transgenic mice exhibit reduced short term plasticity as measured by paired-pulse facilitation in addition to reduced LTP as elicited by high frequency stimulation to the perforant pathway.

  5. X
    Cognitive Impairment at 36

    By 8 months of age, transgenic mice exhibit memory impairment in the Morris water maze compared to mice expressing equivalent levels of wild-type human APP.

Absent
  • Plaques at

    Extracelluar amyloid plaques are not observed out to 24 months; however, Aβ accumulates within neurons of the hippocampus and cerebral cortex starting around eight months of age.

  • Tangles at

    Overt tangle pathology is not observed out to 24 months of age, but abnormal tau phosphorylation is observed starting around eight months of age.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP E693del (Osaka) APP: Transgenic Alzheimer's Disease

Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus.

Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP.

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App KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, App, Trem2 TREM2 R47H APOE: Knock-In; App: Knock-Out; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APP NL-F Knock-in

Observed
  1. X
    Plaques at 26

    Homozygotes develop amyloid plaques starting at 6 months in the cortex and hippocampus. Heterozygotes develop amyloidosis after 24 months. Plaques contained Aβ1-42 and pyroglutamate Aβ (Aβ3(pE)-42); Aβx-40 was a minor species.

  2. X
    Gliosis at 26

    Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.

  3. X
    Synaptic Loss at 39

    Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.

  4. X
    Cognitive Impairment at 78

    Memory impairment in homozygous mice at 18 months as measured by the Y maze test. APPNL/NL mice (with Swedish mutation only) were unimpaired at this age. No significant deficit was seen in the Morris water maze at 18 months.

Absent
  • Tangles at

    Absent; although elevated levels of phosphorylated tau are observed in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP I716F (Iberian) APP: Knock-In Alzheimer's Disease

Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze.

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APP NL-G-F Knock-in

Observed
  1. X
    Plaques at 9

    Aggressive amyloidosis; plaques develop in homozygous mice starting at 2 months with near saturation by 7 months. Aβ deposition at 4 months in heterozygous mice. Cortical and subcortical amyloidosis present.

  2. X
    Gliosis at 9

    Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.

  3. X
    Synaptic Loss at 17

    Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.

  4. X
    Cognitive Impairment at 26

    Memory impairment in homozygous mice by 6 months of age as measured by the Y maze.

Absent
  • Tangles at

    Absent; although phosphorylated tau is elevated in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) APP: Knock-In Alzheimer's Disease

Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 6 months as measured by the Y maze.

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AppNL-G-F/MAPT double knock-in

Observed
  1. X
    Plaques at 8

    Plaques observed at 2 months.

  2. X
    Gliosis at 16

    Astrogliosis and microgliosis observed by 4 months.

  3. X
    Cognitive Impairment at 52

    Deficits in the Y-maze test of working memory at 12 months of age.

Absent
  • Tangles at

    No neurofibrillary tangles observed up to 24 months of age.

  • Neuronal Loss at

    No neurodegeneration observed up to 24 months of age.

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App, MAPT APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) App: Knock-In; MAPT: Knock-In Alzheimer's Disease

Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F.

Deficits in the Y-maze test of working memory, similar to AppNL-G-F.

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APPPS1

Observed
  1. X
    Plaques at 6

    Aβ deposition begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).

  2. X
    Neuronal Loss at 74

    Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).

  3. X
    Gliosis at 6

    Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).

  4. X
    Synaptic Loss at 10

    Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).

  5. X
    Changes in LTP/LTD at 35

    Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).

  6. X
    Cognitive Impairment at 30

    Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).

Absent
  • Tangles at

    Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 L166P APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.

 

Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months.

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APP+PS1

Observed
  1. X
    Plaques at 76

    Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.

  2. X
    Neuronal Loss at 76

    Necrotic neurons in hippocampus and cortex.

  3. X
    Cognitive Impairment at 40

    Deficits in Barnes maze at 10 months.

Absent
No Data
  • Tangles at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP V717F (Indiana), PSEN1 L166P APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age.

Deficits in Barnes maze by 10 months of age.

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APP/PS1/rTg21221

Observed
  1. X
    Plaques at 35

    Cortical plaques observed between 8-10 months. Plaques larger than in control mice not expressing human tau.

  2. X
    Neuronal Loss at 36

    Neuronal loss observed adjacent to plaques relative to more distal areas.

  3. X
    Gliosis at 37

    Increased astrocytosis adjacent to plaques relative to more distal areas.

  4. X
    Synaptic Loss at 40

    Decreased synapse density adjacent to plaques relative to more distal areas.

Absent
  • Tangles at

    No tangles. Aggregates of misfolded and phosphorylated tau observed between 8-10 months.

No Data
  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1, MAPT APP KM670/671NL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease

Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed.

No data.

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APPsw/0; Pdgfrβ+/-

Observed
  1. X
    Plaques at 39

    By 9 months of age APPsw/0;Pdgfrβ+/- mice have an elevated plaque load in the cortex and hippocampus compared with age matched APPsw/0;Pdgfrβ+/+. littermates. They also have extensive cerebral amyloid angiopathy.

  2. X
    Neuronal Loss at 39

    Progressive neuronal degeneration including reduced neurite density and reduced neuronal number in the cortex and hippocampus of APPsw/0; Pdgfrβ+/- mice at at nine months compared to age-matched APPsw/0; Pdgfrβ+/+ littermates.

  3. X
    Cognitive Impairment at 41

    At nine months, APPsw/0;Pdgfrβ+/- mice perform poorly on several hippocampal-dependent behavioral tests including burrowing, nest construction, and novel object recognition, compared with age-matched APPsw/0;Pdgfrβ+/+ littermates.

Absent
No Data
  • Tangles at

    Although mature neurofibrillary tangles were not observed by 9 months (the oldest age assessed), the mice develop significant tau pathology, including tau hyperphosphorylation in cortical and hippocampal neurons. Pre-tangle pathology is observed, including neuronal caspase-cleaved tau, and conformational changes as indicated by the conformation-specific antibody MC1.

  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PDGFRB APP KM670/671NL (Swedish) APP: Transgenic; PDGFRB: Knock-Out Alzheimer's Disease

Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus.

Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition.

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APPSwDI x NOS2 Knock-out

Observed
  1. X
    Plaques at 49

    Aβ deposits by 52 weeks. Particularly dense Aβ immunoreactivity in the subiculum and thalamus, including in the cerebral microvessels (Wilcock et al., 2008).

  2. X
    Tangles at 49

    Extensive tau pathology by 52 weeks, including intraneuronal aggregates of hyperphosphorylated tau. Increased phosphorylated tau in bigenic mice compared to APPSwDI mice (Wilcock et al., 2008).

  3. X
    Neuronal Loss at 52

    Significant neuron loss by 52 weeks in the hippocampus and subiculum, especially of neuropeptide Y neurons. Numerous Fluoro-Jade C+ neurons: 30% loss in the hippocampus, 35% loss in the subiculum (Wilcock et al., 2008).

  4. X
    Cognitive Impairment at 53

    Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).

Absent
No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, NOS2 APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) APP: Transgenic; NOS2: Knock-Out Alzheimer's Disease

Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone.

Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks.

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APP(Swedish) (R1.40)

Observed
  1. X
    Plaques at 59

    By 13.5 months homozygous mice develop both parenchymal and vascular amyloid deposits which first appear in the frontal cortex. No Aβ deposition at 5 months (Lehman et al., 2003).

  2. X
    Gliosis at 61

    Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).

Absent
  • Tangles at

    No mature tangles, but some changes in phosphorylated tau.

  • Changes in LTP/LTD at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease

By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months.

Unknown.

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APPSwe (line C3-3)

Observed
  1. X
    Plaques at 104

    Some plaque formation at advanced age (24-26 months) (Savonenko et al., 2003).

Absent
  • Cognitive Impairment at

    Normal reference and working memory up to 12-14 months on congenic background (Savonenko et al., 2003).

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease

Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age.

Congenic animals showed normal reference and working memory up to 12-14 months.

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APPSwe/PSEN1(A246E)

Observed
  1. X
    Plaques at 39

    By 9 months of age, amyloid plaques develop in the hippocampus and subiculum, later extending to the cortex (Borchelt et al., 1997). The striatum and thalamus are relatively spared out to 18 months of age. Amyloid pathology is more severe in female mice, with a greater amyloid burden measured at 12 and 17 months of age (Wang et al., 2003).

  2. X
    Gliosis at 52

    By one year of age, reactive gliosis is observed in the cortex and hippocampus and is associated with dystrophic neurites (Borchelt et al., 1997).

  3. X
    Cognitive Impairment at 48

    Age-associated cognitive impairment, as measured by the Morris water maze, was observed in 11 to 12-month-old males. Both acquisition and retention were impaired. No impairment at 3-4 months of age. At both time points mice performed normally on a position discrimination task in the T-maze (Puoliväli et al., 2002).

Absent
  • Tangles at

    Not observed.

  • Neuronal Loss at

    There was no difference in neuronal numbers in the cingulate cortex compared with wild-type mice (Xiang et al., 2002).

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 A246E APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus.

Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task.

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APPSwe/PSEN1dE9 (C3-3 x S-9)

Observed
  1. X
    Plaques at 26

    Plaques are present in the hippocampus and cortex by 6 months of age.

  2. X
    Cognitive Impairment at 78

    Age-related cognitive deficits. Episodic memory appears to be more sensitive than reference memory. No differences at 6 months of age, but detectable at 18 months (Savonenko et al., 2005).

Absent
  • Tangles at

    Not observed.

No Data
  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers.

Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months.

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APPswe/PSEN1dE9 (C57BL6)

Observed
  1. X
    Plaques at 16

    Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months.

  2. X
    Gliosis at 17

    Plaque-associated astrogliosis and microgliosis are evident by 4 and 8 months, respectively.

  3. X
    Synaptic Loss at 18

    Synapse loss in the hippocampus occurs by 4 months.

  4. X
    Cognitive Impairment at 40

    Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.

Absent
  • Tangles at

    Not observed.

  • Neuronal Loss at

    Neuron loss has not been observed in mice up to 12 months of age.

No Data
  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina.

Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.

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APPswe/PSEN1dE9 (line 85)

Observed
  1. X
    Plaques at 26

    Occasional Aβ deposits can be found by 6 months, with abundant plaques in the hippocampus and cortex by 9 months (Jankowsky et al., 2004) and a progressive increase in plaques up to 12 months (Garcia-Alloza et al., 2006).

  2. X
    Neuronal Loss at 35

    Neuronal loss observed adjacent to plaques relative to more distal areas.

  3. X
    Gliosis at 26

    Minimal astrocytosis at 3 months; significant astrocytosis by 6 months, especially in areas around plaques. Extensive GFAP+ staining at 15 months and later throughout the cortex (Kamphuis et al., 2012).

  4. X
    Synaptic Loss at 17

    In the B6 congenic mice, age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and Homer immunoreactivity in the hippocampus by 4 months (Hong et al., 2016).

  5. X
    Changes in LTP/LTD at 13

    Transient long-term potentiation (t-LTP) is reduced by 3 months. The degree of impairment is not related to age from 3 to 12 months (Volianskis et al., 2008).

  6. X
    Cognitive Impairment at 52

    Impairment in the Morris water maze at 12 months, specifically during acquisition of the hidden platform sub-task and the probe trial, but not in the visible platform test (Lalonde et al., 2005). At 13 months the mice commit more errors in the Morris water maze, but not at 7 months (Volianskis et al., 2008).

Absent
  • Tangles at

    Not observed.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity.

Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing).

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APP(V642I)KI

Observed
  1. X
    Cognitive Impairment at 117
    Impairments at the water finding task at age 27-29 months, a test of long-term memory. No differences in the open field test of the elevated plus maze indicating no difference in general behavioral patterns, activity level, or emotional state.
Absent
  • Plaques at

    Absent.

  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP V717I (London) APP: Transgenic Alzheimer's Disease

Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.

At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.

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APP(V717I)

Observed
  1. X
    Plaques at 43

    Plaques start in the cortex and subiculum at ~10 months. Diffuse amyloid deposits and compact neuritic plaques at 13-18 months especially in the hippocampus and cortex, with occasional deposits in the thalamus and fimbria, external capsule, pontine nuclei, and white matter (Moechars et al., 1999). Prominent amyloid deposits in brain vessels after 15 months (Van Dorpe et al, 2000).

  2. X
    Gliosis at 43

    GFAP, microglial activation, and other markers of brain inflammation are elevated by 10 months.

  3. X
    Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. X
    Cognitive Impairment at 26

    From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP V717I (London) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression.

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APP(V717I) x PS1(A246E)

Observed
  1. X
    Plaques at 17

    Plaques start in cortex, hippocampus and subiculum at 4-6 months.

  2. X
    Gliosis at 20

    Elevated GFAP, microglial activation, and other markers of brain inflammation increase as of 4.5 months.

  3. X
    Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. X
    Cognitive Impairment at 22

    From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated murine tau, but no tangle pathology.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP V717I (London), PSEN1 A246E APP: Multi-transgene; PSEN1: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology.

From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression.

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Arc48 (APPSw/Ind/Arc)

Observed
  1. X
    Plaques at 9

    Parenchymal neuritic plaques by 2 months with prominent plaque deposition in the hippocampus by 3-4 months. Abundant mature thioflavin-S positive plaques with dystrophic neurites by 10-12 months (Cheng et al., 2007).

  2. X
    Gliosis at 13

    Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).

  3. X
    Cognitive Impairment at 13

    At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.

At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.

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ArcAβ

Observed
  1. X
    Plaques at 39

    Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone (Knobloch et al., 2007).

  2. X
    Changes in LTP/LTD at 15

    LTP is severely impaired in slices from 3.5 and 7.5 month old mice. LTP and basal synaptic transmission were normal in slices from one month old mice (Knobloch et al., 2007).

  3. X
    Cognitive Impairment at 26
    Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze, as well as in active avoidance behavior (Knobloch et al., 2007).
Absent
  • Tangles at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.

Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.

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ARTE10

Observed
  1. X
    Plaques at 13

    Robust and reliable plaque pathology as early as 3 months in homozygotes, 5 months in hemizygotes. Plaques start in the anterior neocortex and subiculum, spreading to other brain regions (e.g. hippocampus, thalamus, amygdala). Congophilic dense-core plaques are abundant, with lower levels of diffuse plaques and some cerebral amyloid angiopathy.

  2. X
    Gliosis at 22

    Glial activation, including reactive astrocytes and activated microglia, is present in areas around plaques by 5 months of age in homozygous animals, later in hemizygotes.

  3. X
    Synaptic Loss at 13

    Decreased expression of synaptophysin mRNA in the brain by 3-4 months of age in both hemizygous and homozygous animals.

  4. X
    Cognitive Impairment at 52

    Select, paradigm-dependent, deficits in learning and memory, especially episodic memory, by 12 months in homozygous and hemizygous mice.

Absent
  • Tangles at

    No tangles or neuropil threads, but some hyperphosphorylated tau by eight months in dystrophic neurites.

  • Neuronal Loss at

    Outright neuronal loss has not been documented, but substantial degeneration of dendritic arbors occurs by 10-14 months of age in hippocampal neurons.

No Data
  • Changes in LTP/LTD at

    Unknown; however, hippocampal neurons exhibit substantial changes in electrophysiological properties by 10-14 months of age, including hyperexcitability in the form of increased firing of action potentials and a more efficient transition from solitary firing to bursting.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 M146V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches.

Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months.

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BACE1 cKO (Hu, Yan) X 5xFAD

Observed
  1. X
    Plaques at 11

    Accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.

  2. X
    Gliosis at 11

    Reactive astrocytes and microglia accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.

  3. X
    Changes in LTP/LTD at 40

    Deficit in LTP at Schaffer collateral–CA1 synapses, but less severe than in control 5xFAD mice.

Absent
  • Cognitive Impairment at

    Cued and contextual fear conditioning normal, tested at eight to 10 months of age.

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter.

Normal contextual and cued fear conditioning, tested at 8 to 10 months of age.

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Bace1 conditional knock-out (adult, whole body) (Vassar)

Observed
Absent
  • Changes in LTP/LTD at

    LTP at Schaffer collateral–CA1 synapses was similar in slices obtained from 12-month BACE1-deficient and control mice.

  • Cognitive Impairment at

    Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning when tested at 9 months of age.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

Defects in axonal organization.

Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations.

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BACE1 conditional knock-out (Hu, Yan)

Observed
  1. X
    Changes in LTP/LTD at 40

    Long-term potentiation at Schaffer collateral–CA1 synapses impaired in slices obtained from 10- to 12-month-old mice.

Absent
  • Plaques at

    Not observed.

  • Tangles at

    Not observed.

  • Neuronal Loss at

    Not observed.

  • Gliosis at

    No astrogliosis at 1-2 months.

  • Cognitive Impairment at

    Contextual and cued fear conditioning normal at 8-10 months.

No Data
  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

No gross morphological changes observed.

BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age.

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Bace1 conditional knock-out (neonatal, forebrain) (Vassar)

Observed
  1. X
    Cognitive Impairment at 24

    Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning.

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

Hypomyelination and defects in axon organization.

Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments.

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BRI-Aβ42 (BRI2-Aβ42)

Observed
  1. X
    Plaques at 13

    Detergent-insoluble amyloid-β and cored plaques as early as three months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices by 12 months. Extensive congophillic amyloid angiopathy.

  2. X
    Gliosis at 13

    Plaque-associated reactive gliosis as measured by GFAP immunostaining.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

  • Cognitive Impairment at

    On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss.

On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

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C9-BAC500 (Brown)

Observed
  1. X
    Cytoplasmic Inclusions at 40

    No cytoplasmic mislocalization, or aggregation of TDP-43 in the motor cortex. However, dipeptide repeats accumulated at advanced age and formed small perinuclear inclusion bodies positive for poly-GP.

Absent
  • Motor Impairment at

    No overt motor deficit as measured by the Rotarod and grip strength.

  • Cortical Neuron Loss at

    Not observed.

  • Lower Motor Neuron Loss at

    Not observed.

  • NMJ Abnormalities at

    No difference in denervation of neuromuscular junctions at 24 months of age. No difference in motor or sensory spinal nerve root axon number or morphology.

  • Body Weight at

    Non-significant trend for male C9BAC mice to be heavier than non-Tg controls. Female data have not yet been reported.

  • Premature Death at

    Normal lifespan beyond 2 years in male mice. Female data have not yet been reported.

  • Gliosis at

    No signs of increased activation of microglia or astrocytes in the brain or spinal cord.

No Data
  • Muscle Atrophy at

    Muscle histology has not been reported, but no overt muscle atrophy was observed.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
C9orf72 Hexanucleotide repeat in C9ORF72 C9orf72: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Widespread RNA foci throughout the nervous system starting at 3 months of age, especially comprised of sense transcript. Dipeptide repeats (e.g., poly-GP) as soluble protein and insoluble aggregates. No neurodegeneration. No TDP-43 aggregation, gliosis, inflammation, or synapse loss.

No overt behavioral abnormalities compared to non-Tg controls. Assessment included grip strength, Rotarod performance, and intruder test.

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C9-BACexp (Baloh/Lutz)

Observed
  1. X
    Cytoplasmic Inclusions at 13

    RNA foci throughout the nervous system starting at 3 months of age. Foci comprised of RNA transcripts in both the sense and antisense directions. Age-associated formation of dipeptide aggregates, e.g., poly-GP.

Absent
  • Motor Impairment at

    No abnormalities in grip strength, Rotarod performance, or open-field testing at a young age (3 months) or advanced age (18 months), compared with non-Tg controls.

  • Cortical Neuron Loss at

    Not observed.

  • Lower Motor Neuron Loss at

    Not observed.

  • NMJ Abnormalities at

    Not observed.

  • Muscle Atrophy at

    Not observed.

  • Body Weight at

    No abnormalities in body weight at a young age (3 months) or advanced age (18 months) compared with non-Tg controls.

  • Premature Death at

    Normal lifespan.

  • Gliosis at

    No increase in GFAP staining in the brain and spinal cord compared with non-Tg controls, even at 18 months of age.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
C9orf72 Hexanucleotide repeat in C9ORF72 C9orf72: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Widespread RNA foci throughout the nervous system first assessed at 3 months of age. Soluble dipeptide repeats (e.g., poly-GP) and insoluble aggregates. No neurodegeneration. No TDP-43 aggregation, gliosis, inflammation, or obvious synapse loss.

No behavioral abnormalities compared to non-Tg controls at either young age (3 months) or advanced age (18 months). Tests included: grip strength, Rotarod performance, open-field, three-chamber, and Y-maze.

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C9ORF72(AAV)(G4C2)149

Observed
  1. X
    Motor Impairment at 24

    Deficits in the hanging wire test emerge between 3 and 6 months.

  2. X
    Cortical Neuron Loss at 24

    Cortical neuron loss by 6 months.

  3. X
    Cytoplasmic Inclusions at 12

    Cytoplasmic inclusions containing dipeptide repeat proteins (DPRs) derived from sense RNA seen in the cortex, hippocampus, cerebellum, and spinal cord; inclusions containing DPRs produced from antisense transcripts seen in the cortex and occasionally in the hippocampus.

  4. X
    Gliosis at 12

    Astrogliosis in the cortex by 3 months.

Absent
No Data
  • Lower Motor Neuron Loss at

    No data.

  • NMJ Abnormalities at

    No data.

  • Muscle Atrophy at

    No data.

  • Body Weight at

    No data.

  • Premature Death at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
C9orf72 Hexanucleotide repeat in C9ORF72 C9orf72: Virus Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Intranuclear foci containing antisense and antisense repeat RNA; cytoplasmic inclusions containing sense and antisense dipeptide repeat proteins; accumulation of phosphorylated TDP-43 and stress granule-associated proteins; neuron loss and gliosis.

Motor and cognitive deficits emerge between 3 and 6 months of age. Hyperactivity seen by 3 months.

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C9ORF72(AAV)(G4C2)66

Observed
  1. X
    Motor Impairment at 26

    At 6 months, 66-repeat mice perform as well as 2-repeat mice on the Rotarod on the first day of testing. However, they fail to improve during subsequent trials, suggesting impairments in coordination and/or motor learning.

  2. X
    Cortical Neuron Loss at 26

    Compared with mice expressing 2-repeats, the 66-repeat mice had 17 percent fewer neurons in the cortex at 6 months of age and 11 percent fewer Purkinje cells in the cerebellum. At this age neurons in the hippocampus and thalamus were not affected.

  3. X
    Cytoplasmic Inclusions at 26

    By 6 months, inclusions of C9RAN dipeptides were present in neurons of the cortex and hippocampus, and to a lesser extent in the cerebellum and spinal cord. Inclusions contained polyGA, polyGP, and polyGR dipeptides and were largely ubiquitin-positive.

  4. X
    Body Weight at 26

    At 6 months females had a lower body weight than mice expressing 2-repeats. Body weight did not differ in males.

  5. X
    Gliosis at 26

    Astrogliosis in the cortex by 6 months.

Absent
  • Lower Motor Neuron Loss at

    At 6 months, neuronal loss in the spinal cord was not detected.

No Data
  • NMJ Abnormalities at

    No data.

  • Muscle Atrophy at

    No data.

  • Premature Death at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
C9orf72 Hexanucleotide repeat in C9ORF72 C9orf72: Virus Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Nuclear RNA foci in neurons, dipeptide aggregates (GA, GP, and GR), cytoplasmic inclusions of phosphorylated TDP-43, neuronal loss, brain atrophy, and gliosis.

Subtle behavioral deficits including anxiety-like behavior, hyperactivity, and antisocial behavior. Subtle motor impairment and failure to improve on the Rotarod.

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C9orf72 Knock-out

Observed
  1. X
    Motor Impairment at 39

    Reduced activity on open-field test. No abnormalities in grip strength or Rotarod performance.

Absent
  • Cortical Neuron Loss at

    Not observed.

  • Lower Motor Neuron Loss at

    Not observed.

  • Cytoplasmic Inclusions at

    Not observed.

  • NMJ Abnormalities at

    Not observed.

  • Muscle Atrophy at

    Not observed.

  • Body Weight at

    Not observed.

  • Premature Death at

    Not observed.

  • Gliosis at

    Not observed.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
C9orf72 C9orf72: Knock-Out Frontotemporal Dementia, Amyotrophic Lateral Sclerosis

Chromatolytic structures are observed with H&E staining, in gray and white matter of the spinal cord. Neurodegeneration not present.

Normal sensorimotor coordination and limb strength. Reduced activity in open-field test.

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CamKII;(GR)80

Observed
  1. X
    Cortical Neuron Loss at 24

    Neuron loss in the cortex, beginning between 3 and 6 months of age.

  2. X
    Gliosis at 24

    Microgliosis and astrogliosis evident at 6 and 9 months, respectively.

Absent
  • Motor Impairment at

    No difference between CamKII;(GR)80 mice and CamKII-tTA control mice up to 9 months of age.

  • Cytoplasmic Inclusions at

    No TDP-43 inclusions seen in mice studied up to 8 months of age.

  • Body Weight at

    No difference between CamKII;(GR)80 mice and CamKII-tTA control mice up to 11 months of age.

No Data
  • Lower Motor Neuron Loss at

    No data, but note that the transgene is not expressed in these neurons.

  • NMJ Abnormalities at

    No data.

  • Muscle Atrophy at

    No data.

  • Premature Death at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Neuron loss in the frontal cortex, beginning between 3 and 6 months of age. Microgliosis and astrogliosis evident at 6 and 9 months, respectively. No TDP-43 inclusions seen in mice studied up to 8 months of age. DNA damage and mitochondrial abnormalities observed.

Deficits in social behavior and increased anxiety emerge between 3 and 6 months. Working memory is intact at least through 9 months of age.

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CAST.APP/PS1

Observed
  1. X
    Plaques at 32

    Thioflavin S-positive amyloid plaques are present in the cortex and hippocampus by 8 months of age, with more severe plaque pathology in females than in males.

  2. X
    Neuronal Loss at 34

    Compared with their non-transgenic littermates, CAST.APP/PS1 mice have fewer neurons in area CA1 of the hippocampus. Cortical neuron numbers do not differ between the genotypes.

  3. X
    Gliosis at 33

    Plaque-associated microgliosis observed by 8 months.

  4. X
    Cognitive Impairment at 31

    Deficits in short-term memory by 8 months in males (data from females unavailable).

Absent
  • Tangles at

    Not observed.

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1.

Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test).

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Ceacam1 KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, Ceacam1, Trem2 TREM2 R47H APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Clasp2*L163P/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Clasp2, APOE, Trem2 TREM2 R47H Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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E2FAD

Observed
  1. X
    Plaques at 17

    Plaques develop in the subiculum and deep cortical layers by 4 months.

  2. X
    Gliosis at 26

    Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

  3. X
    Synaptic Loss at 17

    Protein levels of  NMDA receptor subunits decreased from 2 to 6 months.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    E2FAD mice had performance in learning and memory tasks comparable to E3FAD animals and better than E4FAD mice.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.

In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice.

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E3FAD

Observed
  1. X
    Plaques at 17

    Plaques develop in the subiculum and deep cortical layers by 4 months.

  2. X
    Gliosis at 26

    Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

  3. X
    Synaptic Loss at 17

    Protein levels of  NMDA receptor subunits decreased from 2 to 6 months.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    E3FAD mice had performance in learning and memory tasks comparable to E4FAD and E2FAD animals.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.

In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice.

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E4FAD

Observed
  1. X
    Plaques at 17

    Plaques develop in the subiculum and deep cortical layers by 4 months.

  2. X
    Gliosis at 26

    Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

  3. X
    Synaptic Loss at 17

    Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.

  4. X
    Cognitive Impairment at 8

    Modest learning deficits in the Morris water maze by 2 months. Progressive decrease in performance on learning and memory tasks. 

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. 

Age-dependent learning and memory deficits in the Y maze and Morris water maze.

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Endogenous Sod1 D83G

Observed
  1. X
    Motor Impairment at 6

    Both male and female mice develop a variety of progressive motor symptoms. Grip strength was reduced at 6 weeks of age. Tremors developed by about 5 months of age. Rotarod performance was impaired, at 23 weeks in females and 67 weeks in males.

  2. X
    Cortical Neuron Loss at 29

    Neuronal numbers comparable to wild-type at 15 weeks, but about 20 percent loss of upper motor neurons by 29 weeks. Neurons in layer V of the motor cortex appeared selectively vulnerable.

  3. X
    Lower Motor Neuron Loss at 15

    Neuronal numbers comparable to wild-type at 6 weeks, but loss occurred by 15 weeks. The neuronal loss then stabilized; it was not more severe at 52 weeks of age.

  4. X
    NMJ Abnormalities at 52

    Denervation of a hindlimb muscle, the extensor digitorum longus, was detected by 52 weeks of age, and a decreased number of motor units in the EDL muscle.

  5. X
    Body Weight at 4

    Homozygous mice, both male and female, showed reduced body weight by 4 weeks of age in contrast to wild-type littermates. Loss of excessive body weight was the primary factor leading to euthanasia.

  6. X
    Premature Death at 71

    Males reach end-stage sooner than females (495 ± 22 versus 588 ± 24 days). Animals were sacrificed when weight loss exceeded 20 percent of maximum weight, in accordance with animal-use guidelines. This is likely explained by the development of hepatocellular carcinomas due to SOD1 loss of function.

  7. X
    Gliosis at 15

    Gliosis, of both astrocytes and microglia, was evident in the spinal cord by 15 weeks. It was further elevated at 52 weeks.

Absent
  • Cytoplasmic Inclusions at

    Not observed.

No Data
  • Muscle Atrophy at

    Muscle atrophy was not reported, although changes to the muscle composition and histochemistry were observed.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
SOD1 D83G in SOD1 SOD1: Other Amyotrophic Lateral Sclerosis

Upper and lower motor neuron loss in specific regions (layer V of motor cortex and lumbar spinal cord). Gliosis in spinal cord. Denervation of hindlimb muscle.

Progressive motor impairments, including tremor, gait abnormalities, decreased grip strength, and impaired Rotarod performance.

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FUSΔ14 (FUSd14)

Observed
  1. X
    Cytoplasmic Inclusions at 13

    Neuronal cytoplasmic inclusions were present by 3 months of age in the cerebral cortex. Inclusions occurred in about 20% of neurons and often co-labeled with ubiquitin.

Absent
  • Motor Impairment at

    When the mice were sacrificed at 3 months of age, they appeared healthy and displayed no obvious motor phenotype.

  • Cortical Neuron Loss at

    Not observed.

  • Lower Motor Neuron Loss at

    Not observed.

  • Gliosis at

    No obvious astrogliosis or microglial activation at 3 months of age in the cerebral cortex.

No Data
  • NMJ Abnormalities at

    No data.

  • Muscle Atrophy at

    No data.

  • Body Weight at

    No data.

  • Premature Death at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
FUS FUS Δ14 FUS: Virus Frontotemporal Dementia, Amyotrophic Lateral Sclerosis

Widespread neuronal cytoplasmic inclusions (NCIs) by 3 months of age. Inclusions were FUS-positive and often co-labeled with ubiquitin.  No overt neurodegeneration or reactive gliosis.

No overt motor phenotypes at 3 months of age.

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FUSDelta14 Knock-in

Observed
  1. X
    Motor Impairment at 65

    Normal motor activity at 3 months of age but impaired hindlimb function by 15 months.

  2. X
    Lower Motor Neuron Loss at 50

    No lower motor neuron loss at 3 months but 14% reduction in the number of motor neurons in lumbar spinal cord at 12 months and 20% reduction by 18 months.

  3. X
    NMJ Abnormalities at 78

    Reduction in the number of intact neuromuscular junctions (fully innervated endplates) in hindlimb lumbrical muscles by 18 months of age.

  4. X
    Premature Death at 82

    Reduced survival starting at 19 months of age.

Absent
  • Cytoplasmic Inclusions at

    No increase in the number of spinal motor neurons that contain p62- or ubiquitin-positive inclusions in aged FUSDelta14 mice compared with aged wild-type mice.

No Data
  • Cortical Neuron Loss at

    No data.

  • Muscle Atrophy at

    No data.

  • Body Weight at

    No data.

  • Gliosis at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
FUS FUSDelta14 truncation mutation FUS: Knock-In Amyotrophic Lateral Sclerosis

Progressive (not developmental) loss of lumbar spinal motor neurons, starting by 12 months of age; partial denervation of hindlimb muscles. Mislocalization of mutant FUS from nucleus to cytoplasm.

Hindlimb motor impairment by 15 months.

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FusΔNLS

Observed
  1. X
    Motor Impairment at 0

    By 10 months, mice demonstrated irregular walking patterns and reduced hang time on the inverted grid test. No deficits in grip strength or rotarod performance. Paralysis was not observed.

  2. X
    Lower Motor Neuron Loss at 0

    Approximately 30% reduction of motor neuron numbers in the dorsal spinal cord.

  3. X
    Cytoplasmic Inclusions at 0

    Ubiquitin pathology was observed in motor neurons, but p62 inclusions were not.

  4. X
    NMJ Abnormalities at 0

    Fibrillation and fasciculation potentials were observed in the gastrocnemius or tibialis anterior muscles. There was also a reduction in compound muscle action potential amplitude.

  5. X
    Gliosis at 0

    Slight increase in oligodendrocytes in the spinal cord white matter.

Absent
  • Body Weight at

    By 22 months, no weight loss was observed.

  • Premature Death at

    Life span was not altered.

No Data
  • Cortical Neuron Loss at

    No data.

  • Muscle Atrophy at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Fus FUS ΔNLS Fus: Knock-In Amyotrophic Lateral Sclerosis

The spinal cord exhibited FusΔNLS mislocalization, a loss of motor neurons, and ubiquitin pathology.

No impairments in grip strength or rotarod performance. Irregular walking patterns and reduced hang time on inverted grid test were observed.

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FUS-R521C

Observed
  1. X
    Motor Impairment at 0

    Early postnatal motor impairment, including abnormal hindlimb clasping when lifted by the tail, gait abnormalities, and impaired Rotarod performance.

  2. X
    Lower Motor Neuron Loss at 2

    No detectable difference in spinal motor neurons at P0. At P16, about 20% loss of ChAT-positive neurons in the anterior horn of cervical spinal cord. At P30-P60, about 50% loss of anterior horn neurons. Remaining motor neurons show reduced dendritic complexity and synaptic density.

  3. X
    Cytoplasmic Inclusions at 0

    Less than 10% of spinal motor neurons have cytoplasmic FUS inclusions.

  4. X
    NMJ Abnormalities at 0

    Reduced innervation of neuromuscular junctions in the diaphragm.

  5. X
    Muscle Atrophy at 0

    The majority of mice have severe skeletal muscle atrophy in the hindlimb by end stage.

  6. X
    Body Weight at 0

    Early postnatal growth is retarded, and the mice experience progressive loss of body weight.

  7. X
    Premature Death at 0

    The majority of mice in the N1F1 generation reached end stage and were sacrificed by postnatal day 100. Mice in subsequent generations live longer: about 40% reach end stage by postnatal day 200.

  8. X
    Gliosis at 0

    Prominent increase in microgliosis and astrogliosis in the anterior horn of the spinal cord by end stage.

Absent
  • Cortical Neuron Loss at

    No detectable loss of cortical neurons; however, neurons in the sensorimotor cortex show reduced dendritic complexity and reduced synaptic density.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
FUS FUS R521C FUS: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Robust neurodegeneration in the anterior horn of the spinal cord, including about 50% loss of neurons by end stage. Prominent microgliosis and astrogliosis in the anterior horn at end stage. Very rare cytoplasmic FUS inclusions.

A variety of motor impairments from a young age, including spastic paraplegia, abnormal hindlimb clasping, gait abnormalities, and impaired performance on the Rotarod.

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hAbeta-loxP-KI

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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hAPP/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, Trem2 TREM2 R47H APOE: Knock-In; APP: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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hCR1 KI on APOE4/Trem2

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Cr2, CR1, CR2, APOE, Trem2 TREM2 R47H Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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hFUS-P525L

Observed
  1. X
    Motor Impairment at 0

    Deficits in wire hang test at 360 days.

  2. X
    Lower Motor Neuron Loss at 0

    Progressive loss of motor neurons at lumbar level 5.

  3. X
    NMJ Abnormalities at 0

    Progressive denervation of hindlimb muscles. Decreased density of synaptic vesicles and mitochondria with normal morphologies. Altered electrophysiological properties.

  4. X
    Muscle Atrophy at 0

    Reduced fiber diameter in the tibialis anterior muscle.

  5. X
    Gliosis at 0

    Astrocytosis and microgliosis were observed in the spinal cord.

Absent
  • Cytoplasmic Inclusions at

    No FUS inclusions were observed.

  • Premature Death at

    Not observed by 360 days.

No Data
  • Cortical Neuron Loss at

    No data.

  • Body Weight at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
FUS FUS P525L FUS: Knock-In Amyotrophic Lateral Sclerosis

Progressive loss of spinal cord motor neurons associated with muscle denervation and reduced muscle fiber diameter. Gliosis in spinal cord. Abnormal mitochondrial morphologies. Mutant FUS mislocalized to cytoplasm.

Deficits in wire hang test at 360 days.

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hFUS (+/+) (PrP-hFUS)

Observed
  1. X
    Motor Impairment at 4

    Homozygous mice exhibited motor symptoms at four weeks of age, starting with a tremor and mild signs of hindlimb dysfunction, including gait abnormalities. Motor symptoms progressed quickly, ultimately developing into hindlimb paralysis.

  2. X
    Lower Motor Neuron Loss at 11

    By end stage (~11 weeks), homozygous mice had lost about 60 percent of α-motor neurons in the anterior horn of the lumbar spinal cord.

  3. X
    Cytoplasmic Inclusions at 11

    By end stage, cytoplasmic FUS inclusions, described as “granular” and “globular,” develop in the spinal cord of homozygous mice. Ubiquitin-positive inclusions also develop, but do not co-localize with FUS inclusions. Neurons in the brain also develop “granular” and “skein-like” FUS inclusions.

  4. X
    NMJ Abnormalities at 10

    Homozygous mice had about 20 percent fewer functional motor units in the extensor digitorum longus muscle as estimated by neurophysiological assessment.

  5. X
    Muscle Atrophy at 11

    Muscle histology from end stage (~11 weeks) homozygous mice showed focal muscle atrophy in hindlimb muscles.

  6. X
    Body Weight at 4

    Homozygous mice fail to gain weight normally starting about four weeks of age. Their body weight declines in subsequent weeks, often precipitating euthanasia.

  7. X
    Premature Death at 12

    Homozygous mice were euthanized between 10 and 13 weeks of age when they developed severe motor impairment or lost 25 percent of their body weight. Average survival was 82 ± 12 days.

  8. X
    Gliosis at 11

    By end stage (~11 weeks), homozygous mice had microgliosis and astrogliosis in the anterior horn of the spinal cord and in the white matter of the dorsal columns. Reactive gliosis was absent in the brain, despite cytoplasmic inclusions of FUS in some neurons.

Absent
  • Cortical Neuron Loss at

    In the brain, overt neuronal loss was absent at end stage (~11 weeks).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
FUS FUS: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

FUS accumulation in the cytoplasm, including cytoplasmic inclusions in neurons of the brain and spinal cord. Degeneration of spinal motor neurons (~60% by end stage) with astrogliosis and microgliosis.

Severe motor impairment, starting as tremor and gait abnormalities, and progressing to impaired performance on the Rotarod and reduced locomotion. Ultimately hindlimb paralysis and inability to lift the pelvis.

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hFUS-R521C

Observed
  1. X
    Lower Motor Neuron Loss at 0

    Progressive loss of motor neurons at lumbar level 5.

  2. X
    NMJ Abnormalities at 0

    Progressive denervation of hind limb muscles. 

  3. X
    Gliosis at 0

    Astrocytosis and microgliosis were observed in the spinal cord.

Absent
  • Cytoplasmic Inclusions at

    No FUS inclusions were observed.

  • Premature Death at

    Not observed by 360 days.

No Data
  • Motor Impairment at

    No data.

  • Cortical Neuron Loss at

    No data.

  • Muscle Atrophy at

    No data.

  • Body Weight at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
FUS FUS R521C FUS: Knock-In Amyotrophic Lateral Sclerosis

Progressive loss of spinal cord motor neurons associated with muscle denervation. Gliosis in spinal cord. Mutant FUS mislocalized to cytoplasm.

No data.

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hPFN1-G118V

Observed
  1. X
    Motor Impairment at 0

    Progressive motor impairments began ~ 120 days. Mice demonstrated tremors, limb clasping, muscle weakness, gait abnormalities, as well as reduced locomotion and decreased performance on the Rotarod. 

  2. X
    Cortical Neuron Loss at 0

    At 202 days, there was a decrease in the number of corticospinal neurons of the motor cortex.

  3. X
    Lower Motor Neuron Loss at 0

    Progressive loss of ventral horn neurons from 165 through 202 days of age.

  4. X
    Cytoplasmic Inclusions at 0

    Spinal cord motor neurons had TDP-43 puncta.

  5. X
    NMJ Abnormalities at 0

    Denervation of gastrocnemius muscle at end stage. Muscle action potential also had reduced amplitude.

  6. X
    Muscle Atrophy at 0

    At 165 days, hind limb muscle atrophy was observed.

  7. X
    Body Weight at 0

    Body weight peaked ~ 150 days and then progressively decreased.

  8. X
    Premature Death at 0

    Mice were sacrificed at an average of 202 days when they were unable to right themselves. Females on average reached 191 days while males attained 213 days.

  9. X
    Gliosis at 0

    Astrocytosis and microgliosis were observed in the spinal cord at end stage.

Absent
No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
PFN1 PFN1 G118V PFN1: Transgenic Amyotrophic Lateral Sclerosis

Motor neuron loss in the spinal cord associated with muscle denervation and atrophy. Gliosis in spinal cord. Loss of corticospinal neurons of the motor cortex. Aggregates of TDP-43 in spinal motor neurons.

Progressive motor impairments. Minor hind limb posture changes begin at 120 days. Paralysis occurred on average by 165-210 days.

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htau

Observed
  1. X
    Tangles at 39

    Aggregated tau and paired helical filaments detectable at nine months by immunoelectron microscopy, although paired helical filaments of aggregated insoluble tau can be isolated from brain tissue as early as two months. Tau first redistributes from axons to cell bodies. Hyperphosphorylated tau begins to accumulate by six months, and increases further by 13 and 15 months (Andorfer et al., 2003).

  2. X
    Neuronal Loss at 43

    Decrease in cortical thickness and reduced cell number between 10 and 14 months of age. Increased ventricle size increased from age eight months to 18 months. Decrease in the thickness of the corpus callosum (Andorfer et al., 2005).

  3. X
    Changes in LTP/LTD at 52

    In hippocampal slices, LTP induced by high frequency stimulation (HFS) was normal at four months but abolished by 12 months. LTP induced by theta burst stimulation (TBS) was normal at both ages. Paired-pulse ratio (PPR) was unaffected at four months, but increased at 12 months compared with controls, suggesting a decrease in probability of transmitter release (Polydoro et al., 2009).

  4. X
    Cognitive Impairment at 26

    Abnormal spatial learning in six-month-old mice compared with control mice (Phillips et al., 2011). Normal object recognition and spatial learning and memory by MWM at four months, but deficits by 12 months (Polydoro et al., 2009). Impaired burrowing relative to control mice occurs by four months (Geiszler et al., 2016).

Absent
No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT: Knock-Out; MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss.

Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009). 

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hTau-A152T

Observed
  1. X
    Neuronal Loss at 87

    Neuron loss in the hippocampus was observed by 20 months.

  2. X
    Gliosis at 17

    Astrocytosis, but no differences in microglia.

  3. X
    Cognitive Impairment at 74

    In the Morris water maze, performance was impaired after 17 months of age. Nest building was impaired at 10-14 months. Social interaction, anxiety, exploratory behavior, and motor functions were unaltered.

Absent
  • Tangles at

    Abnormal accumulations of soluble tau were observed, but not tangles or tangle-like structures.

  • Changes in LTP/LTD at

    Unchanged at 20 months.

No Data
  • Plaques at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT A152T MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus.

Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal.

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hTau-AT (hTau40-AT)

Observed
  1. X
    Tangles at 13

    Tangles in hippocampus, cortex, and spinal cord starting at 3 months with age-dependent increases. Hyperphosphorylation, conformation changes, and mislocalization.

  2. X
    Neuronal Loss at 52

    Neuron loss in the hippocampus and cortex at 12 months.

  3. X
    Gliosis at 43

    Astrocytosis and microgliosis at 10 months.

  4. X
    Synaptic Loss at 87

    Synaptophysin, but not PSD95, decreased in hippocampus and cortex at 12 months. By Golgi staining, spines unchanged in CA1 at 10 months, increased in CA3 at 12 months, and decreased in CA1 and CA3 at 16 months.

  5. X
    Cognitive Impairment at 70

    No change at 10 months but at 16 months deficits in learning and memory (Morris water maze).

Absent
  • Changes in LTP/LTD at

    Unchanged at 12 months.

No Data
  • Plaques at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT A152T MAPT: Knock-In Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses.

Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal.

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hTau.P301S

Observed
  1. X
    Tangles at 17

    Neurofibrillary tangles detected as early as 4 months of age.

  2. X
    Neuronal Loss at 13

    Neuronal loss starting at 3 months. Loss is especially prominent in the spinal cord with notable loss of superficial cortical neurons as well (Hampton et al., 2010).

  3. X
    Gliosis at 22

    Astrocytosis, as measured by GFAP reactivity, in 6 month-old animals. Microglial activation in the brain stem and spinal cord of 5 month-old animals by OX42 staining (Bellucci et al., 2004).

  4. X
    Cognitive Impairment at 11

    Memory deficit starting at 2.5 months as assessed by the Morris water maze (Xu et al., 2014), but no deficit at 2 months (Scattoni et al., 2010).

Absent
  • Plaques at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301S MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis.

Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months.

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hTDP-43ΔNLS

Observed
  1. X
    Motor Impairment at 1

    Spastic motor impairment indicated by an abnormal clasping response as early as one week after transgene induction. A variety of motor deficits develop by one month after transgene induction, including impaired coordination on the Rotarod and decreased grip strength.

  2. X
    Cortical Neuron Loss at 4

    Severe neuronal degeneration in the dentate gyrus and deep layers of the neocortex. Other regions, such as the hippocampal CA1 subfield and olfactory bulb, were relatively resistant to neurodegeneration. Approximately 50 percent of dentate gyrus neurons were lost one month after the transgene was activated.

  3. X
    Gliosis at 4

    Severe astrogliosis and microgliosis in areas affected by neurodegeneration, including cortical and hippocampal regions, as well as the corticospinal tract.

Absent
  • Lower Motor Neuron Loss at

    Not observed.

  • Cytoplasmic Inclusions at

    High levels of cytosolic TDP-43 but only very rare aggregates (observed in less than 1 percent of cortical neurons and even rarer in other brain regions, such as the hippocampus and striatum).

  • Muscle Atrophy at

    Not observed.

  • Premature Death at

    Not observed.

No Data
  • NMJ Abnormalities at

    Unknown.

  • Body Weight at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
TARDBP TARDBP: Transgenic Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Severe neuronal loss and gliosis in the dentate gyrus and deep cortical layers. Only very rare cytoplasmic aggregates of TDP-43 despite high levels of cytosolic protein. Degeneration of the corticospinal tract, but no lower motor neuron loss or muscle atrophy.

A variety of motor, cognitive, and social deficits, including abnormal clasping response, impaired coordination on the Rotarod, decreased grip strength, impaired recognition and spatial memory, and decreased social behavior. Cognitive and motor impairments largely reversible in young mice following short-term transgene suppression.

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Il1rap KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, Il1rap, Trem2 TREM2 R47H APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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J20 (PDGF-APPSw,Ind)

Observed
  1. X
    Plaques at 22

    At 5-7 months of age diffuse amyloid-β plaques deposit in the dentate gyrus and neocortex. Amyloid deposition is progressive with widespread plaques by 8-10 months. Aβ puncta are deposited in the hippocampus as early as 1 month (Hong et al., 2016).

  2. X
    Neuronal Loss at 12

    Cell loss varies by brain region. No significant neuronal loss was observed in the CA3 region of the hippocampus at 6, 12, 24 and 36 weeks of age nor in the CA1 region at 6 weeks; however, at 12, 24, and 36 weeks significant neuronal loss was observed in the CA1 region compared to age-matched wild-type animals (Wright et al., 2013).

  3. X
    Gliosis at 24

    At 24 and 36 weeks a significant increase in the number of reactive GFAP+ astrocytes and CD68+ microglia was observed in the hippocampi of J20 mice compared to age-matched wild-type controls. No significant difference was observed at 6 and 12 weeks (Wright et al., 2013).

  4. X
    Synaptic Loss at 15

    Age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and homer immunoreactivity in the hippocampus by 3 months; synapse loss was confirmed by electron microscopy. No significant difference was seen at 1 month (Hong et al., 2016).

  5. X
    Changes in LTP/LTD at 13

    Basal synaptic transmission is impaired between 3-6 months; extracellularly recorded field EPSPs at the Schaffer collateral to CA1 synapse in acute hippocampal slices were on average smaller in amplitude than those seen in wild-type mice. Significant deficits in LTP at the Schaffer collateral–CA1 synapse compared with control mice at 3-6 months (Saganich et al., 2006).

  6. X
    Cognitive Impairment at 16

    Deficits in spatial memory and learning appear as the mice age. By 4 months, J20 mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013) and Morris water maze (Cheng et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity.

Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.

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JNPL3(P301L)

Observed
  1. X
    Tangles at 20

    Neurofibrillary tangles develop in an age and gene-dose dependent manner; as early as 4.5 months in homozygotes and 6.5 months in heterozygotes. Tangles and Pick-body-like neuronal inclusions in the amygdala, septal nuclei, preoptic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord (Lewis et al., 2000).

  2. X
    Neuronal Loss at 43

    Neuronal loss, especially in the spinal cord, most prominent in the anterior horn (Lewis et al., 2000).

  3. X
    Gliosis at 43

    Astrogliosis (as measured by GFAP reactivity) in brainstem, diencephalon, and basal telencephalon by 10 months (Lewis et al., 2000).

Absent
  • Plaques at

    Absent.

No Data
  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease

Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord.

By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization.

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Kif21b*T82T/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Kif21b, APOE, Trem2 TREM2 R47H Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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MAPT knock-in

Observed
Absent