Updated 19 February 2008

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Name/ Symbol Strain Name Transgene/ Promoter and Regulatory Elements Genetic Background Behavioral  Phenotype Neurological  Characteristics Patents/  Availability Primary  Citation APPArcSwe Symbol: APP Posted 02/19/08 C57BL/6J-CBA-F1 Human APP cDNA clone with artic mutation (E693G) and Swedish mutation (KM670/671N)/modified Kozak seq/murine Thy-1 promoter. Origin: C57BL/6J-CBA; Background: C57Bl/6J; Backcross five generations. Spatial learning deficits at 4-8 months of age in MWM. Inclusion of the Artic mutation results in enhanced accumulation of soluble Aβ aggregates, facilitated accumulation of Aβ inside neurons and more robust senile plaques. PCT WO2005/089539; Assignee BioArctic Neuroscience. Non-commercial use: Contact Lars Nilsson, lars.nilsson@pubcare.uu.se Phone: +46 18 471 5039. fax: +46 18 471 4808 Uppsala University, Sweden Commercial use: Pär Gellerfors, BioArctic Neuroscience AB, Sweden Phone: +46 8 695 6930 http://www.bioarctic.se Lord et al., 2006 APPPS1 Symbol: APP Posted 05/06/07 B6-Tg(Thy1-APPswe; Thy1-PS1 L166P) Pronuclei coninjected with Thy1-APPKM670/671NL and Thy1-PS1L166P constructs, integration site on the lower arm of chr 2 between 40 and 60 cM C57BL/6J N/A APPPS1 develops cerebral amyloidosis at 6-8 weeks, Aβ 42 >> Aβ 40. Contact Mathias Jucker, mathias.jucker@uni-tuebingen.de Radde et al., 2006 TetO-APPSwe/Ind (line 885) Symbol: APP Posted 01/31/07 B6C3-Tg(tetO-APPswe/ind)8-85Dbo/J Chimeric mo/hu APP695(Swe/Ind) x tetO/ C57BL/6J X C3HeJ F2. Origin founder line 85-5, male hemizygous x female B6C3F1/J. Hemizygous mice viable/fertile. Bigenic mice have 10-fold more activity. Activity abolished by rearing with doxycycline. Mo/huAPP protein at 10-30 fold over endogenous. Treatment with doxycycline inhibits APP expression by >95% and reduces Aβ production. Plaques at 6 months. The Jackson Lab, available, stock #006004. For research or non-commercial use only; tet-system licence may be required. Jankowsky et al., 2005 Amyloid β (A4) precursor protein-binding, family B, member 1 (Apbb 1) Symbol: p97FE65 Posted 01/23/07 B6.129-Apbb1tm1Quhu/J 500bp frag with first 3 start codons in exon 2 replaced by PKG promoter neo-cassette/R1 ES cells/C57BL/6. Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; backcross C57BL/6J Gen >10. Viable and normal, no physical abnormalities. Null mice have slower learning rates in aversive/spatial memory tasks. p97 protein not expressed in null mice, p60 N-term truncated isoform four- to fivefold greater levels. The Jackson Lab, available, stock #005708 Wang et al., 2004 APPSWE (2576) Symbol: APP Updated 1/25/06 B6;SJL -Tg (APPSWE) 2576Kha   Human AP695 cDNA with KM670/671NL/ hamster prion protein gene promoter C57BL/6. Currently breeding hemizygous males with B6SJLF1 females Memory deficits seen in 9-10 month old tg mice. Numerous Aβ plaques, oxidative lipid and glycoxidative damages  Patent: 5,877,399 Taconic Datasheet Hsiao K et al., 1996 Human BACE Symbol: BACE Posted 6/13/2005   Human wtBACE-1 cDNA /mouse Thy 1/microinjected DBA/C57BL/6 embryos. Origin: FVB. Background C57BL/J   Transgene expressed in neurons only. Line 16 had high expression of human BACE. Frozen embryos stored at Charles River Breeding Labs. Contact: Michael Willem Willem et al., 2004 APPSw Symbol: APP Posted 6/7/2005 Tg.AD147.71H Human APPK670N, M671L (Swedish), mThy1.2. Origin: C57BL/6, DBA/2. Backcrossed C57BL/6 for 3N, then intercrossed F13.   Amyloidosis in the 2nd year of life, Amyloidosis 4X more prominent in females than males. Congophilic plaques in cortex and hippocampus, brain Aβ42 levels are 10 fold lower than Aβ40 levels. Contact: Laurence Ozmen Laurence.ozmen@roche.com Richards et al., 2003 hAPPSw/Ind/Arctic Symbol: APP Posted 4/21/2005   Arctic (E22G), Swedish, and Indiana mutations human APP/PDGFß promoter Origin: C57BL/6Hsd; Background C57BL/6J; Generation Arc6 - N5 and Arc48 - N3 Pending Arctic mice form amyloid plaques faster and more extensively than J20 mice, even though they had lower Aβ 1-42/1-40 ratios. Relative levels of hAPP and of the β-secretase-generated C99 fragment were lower in Arc6 and higher in Arc48 than in J20 mice. Contact Lennart Mucke Lmucke@gladstone.ucsf.edu Cheng et al., 2004 APPSw-NSE Symbol: APP Posted 2/5/2005   CMVAPP695sw construct, containing APPsw695/rat pNSE-CAT promoter / NSE-APPsw with the prokaryotic sequence eliminated. Origin: C57BL/6 x DBA/2, Background C57BL/6, Backcross 5 generations At 12 months showed longer escape latencies and increased escape distances in water maze. At 12 months increased Aβ-42 staining without plaque formation. Tau phosphorylation enhanced, JNK and p38 activated. Cox-2 levels, Caspase-3 and TUNEL staining seen. Patent filing date: 11/4/02 Contact: Yong K Kim kimyongkyu@hanmail.net Hwang et al., 2004 APP695K612V or SβCK612V Symbol: APP Posted 12/18/2004   Valine substituted for lysine at site of βAPP/cytomegalovirus enhancer and chicken β-actin promoter. OE C99 Origin: C57BL/6 x C3H. Backcrossed to C57BL/6 Generation 4 (1998)   No brain lesions or plaque formation. 9-13 month old mice show 5x expression of protein product in muscle. Dr. Lee-Way Jin. These mice are no longer available Jin et al., 1998 Down syndrome model; segmental trisomy 16 Symbol: Ts(1716)65Dn Posted 10/26/2004 B6EiC3Sn a/A-Ts(1716)65Dn 3 copies of mouse APP/Translocation of distal end of mouse Chr 16 to Chr 17. Origin: C57Bl/6Jeicher×C3H/HeSnJ. N37 Mice live until adult age. Low birth weight, developmental delay, muscle trembling, male sterility, reduced learning. APP elevated in cerebral cortex. At 6 months, higher level of Aß in hippocampus and mice show decline in cholinergic phenotype and cognitive deterioration. The Jackson Lab, Stock #001924 Davisson et al., 1990 APP-C99 (tg13592) Symbol:APP Posted 10/2/04   5 copies C99 of b-APP /cytomegalovirus enhancer/b-actin promoter /C57BL/6 x DBA/2 Crossed to C57BL/6J >10 Generations Mice exhibit hypoactivity and spatial learning deficit. From 6-12 months display Aβ-immunoreactive deposits within the skeletal muscle fibers. Availability: Contact Dr. Ken-ichiro Fukuchi Fukuchi et al., 1996 APPV642IKI Symbol:APP Posted 8/10/04   APPV642I/ 'knock-in' technique of homologous recombination and Cre-loxP system/Clone R34C(30)-9. Origin: C57BL/6 x CBA and CD-1 Significant deterioration of long-term memory. Acquisition of spatial memory slightly affected, but no deterioration in short-term working memory. 2yr old mice show no neuritic plaques or neurofibrillary tangles, but increases in amount of β-amyloid Aβ42 (43) compared to Aβ40. US Patent Application No.60/482,021 and PCT/JP2004/002296 Availability: Contact Dr Masaaki Matsuoka Kawasumi et al., 2004 A -R1.40 Symbol:APP Posted 12/15/03 A.Cg -Tg (APP)R1.40Lmb YAC with 300 kb hAPPSwe gene/R1 ES cells. Origin: 129X1/SvJ x 129S1/Sv-+P+Tyr-cKitlS1-J/+ Background A/J, N12 N/A Under analysis Bruce Lamb Unpublished B6 -R1.40 Symbol:APP Posted 12/15/03 B6.Cg -Tg (APP)R1.40Lmb YAC with 300 kb hAPPSwe gene/R1 ES cells Origin: 129X1/SvJ x 129S1/Sv-+P+Tyr-cKitlS1-J/+ Background C57BL/6J, N22 N/A Highest-level Aβ 40/42 compared to D2-R1.40 and 129S1-R1.40 mice. Aβ deposits in frontal and parietal cortex of >1-year-old mice Bruce Lamb Lamb BT, et al., 1997 B6 -Py8.9 Symbol:APP Posted 12/15/03 B6.Cg -Tg (APP)Py8.9Lmb YAC with 300 kb hAPP gene/R1 ES cells Origin: 129S2/SvPas Background C57BL/6J, N22 N/A Mice express hAPP transcripts and proteins at levels similar to endogenous mouse. No evidence of AD-type pathology Bruce Lamb Lamb BT et al, l993. D2 -R1.40 Symbol:APP Posted 12/15/03 D2.Cg -Tg (APP)R1.40Lmb YAC with 300 kb hAPPSwe gene/R1 ES cells Origin: 129X1/SvJ x 129S1/Sv-+P+Tyr-cKitlS1-J/+ Background DBA/2J, N22 N/A Lowest level of Aβ 40 and Aβ 42 compared to B6-R1 Bruce Lamb Lamb BT et al, 2003 129S1 -R1.40 Symbol:APP Posted 12/15/03 129S1.Cg -Tg (APP)R1.40Lmb YAC with 300 kb hAPPSwe gene/R1 ES cells Origin: 129X1/SvJ x 129S1/Sv-+P+Tyr-cKitlS1-J/+ Background 129S1/SvImJ, N20 N/A Lower amts of APP CTFs, intermediate levels of Aβ40 and Aβ42 and equivalent levels of holo-APP compared to D2- and B6-R1.4 mice Bruce Lamb Lamb BT et al, 2003. Amyloid β(A4) precursor-like protein 2 Symbol:Aplp2 Updated 12/10/05 B6.129S7-Aplp2tm1Dbo/J inactivated Aplp2 gene by deleting 1.1kb segment/PGKneo cassette/AB2.1 ES cells. Origin: B6;129S7; Backcross C57BL/6J for 5 generations (7/01). No behavioral abnormalities No Aplp2 gene product (mRNA or protein) is detected. Available See JAX datasheet: Stock#: 004142 von Koch et al., 1997 APPnull; Amyloid β (A4) precursor protein Symbol:App Updated 12/10/05 B6.129S7-Apptm1Dbo/J Inactivated Mouse APP gene/ PGKneo targeting vector/AB2.1 ES cells. Origin B6;129S7. Backcross C57BL/6J. Homozygous mice are viable, no physical or behavioral abnormalities at birth. By 14 weeks decreased locomotor activity. At birth no App gene product detected,14 weeks the mice exhibit evidence of reactive gliosis. Available See JAX datasheet Stock#: 004133 Zheng et al., 1995 APP -C100   Human APP695 cDNA Carboxy terminal 100 a.a./ dystrophin neural promoter C58BL/6 x SJL  homozygous Tg showed significant deficits in cued, spatial and reversal performance.  age-dependent impairment of spatial learning. age-dependent neuronal and synaptic degeneration, irregular cytoplasmic accumulations of atypical secondary lysosomes, and an increased neurofilament concentration in unmyelinated axons 5,672,805, 5,849,999, 5,894,078 Contact Rachael Neve These mice are no longer available. Neve RL et al., 1996 APP Flemish/ APPDutch   Human APP770 cDNA with A682G/ Human APP770 cDNA with E693Q/ mouse thy-1 gene promoter FVB/N differential glutamatergic responses, increased aggression, occasional spontaneous seizures and variable premature death significantly decrease α-secretase APP while increasing β-secretase cleaved C-terminal fragments. Aβ level remains low without formation of amyloid plaque. Unpatented Contact Paul Van Dun These mice are no longer available. Kumar-Singh et al., 2000 B6 -J1-96 Symbol:APP Updated 12/15/03 B6.Cg-Tg(APP)J1.96Lmb YAC with 300 kb hAPPSwe/London gene/J1 ES cells Origin: 129S4/SvJae; Background C57BL/6J, N22 N/A High levels of Aβ peptides in tg with Swe and London mutations. A total and 42/43 are elevated in tg with London mutation. Contact B.T. Lamb Lamb BT, et al., 1997 APP London V717I Updated 5/27/05   Human APP695 cDNA with V717I/ mouse thy-1 gene. The thymus specific regulatory elements in intron 3 are thereby deleted, making the resulting promoter "neuron-specific" FVB/N decreased exploration, increased neophobicity, increased male aggressivity amyloid plaques and cerebrovascular angiopathy - onset 10-12 months, cholinergic fiber distortion Unpatented Contact Paul Van Dun Moechars D et al., 1999 NORBA   signal peptide and 99 residues of CTF of bAPP under control of cytomegalovirum enhancer/chicken b-actin promoter. 2000 copies of bA-NOR b were microinjected into one pronucleus of fertilized B6C3F1 x C57BL/6N hybrid eggs N/A Aβ was detected biochemically in brain, kidney, and pancreas with the largest amount present in Pancreas. over 30 times Aβ accumulation in transgenic plasma than in normal human plasma. Contact Mikio Shoji Kawarabayashi et al., 1996 PDGF -APPWT (See JAX datasheet) Symbol:App Updated 11/12/03 B6.Cg-Tg(PDGFB-APP)5Lm/J APPInd tg sequence converted to wildtype by PCR primer modification/PDGFB promoter/(v-sis) oncogene homolog. Origin:C57BL/6 X DBA/2 F1. Backcross C57BL/6J. Maintained as hemizygote   Transgene expression in cerebral neurons, neocortex and hippocampus, with total Aβ levels and 42 Aβ levels lower than in the APP SwInd mutant line. No amyloid plaques up to 24 months of age Available The Jackson Lab Stock#: 004662 Mucke et al., 2000 PDAPP SwInd(J20) Symbol:App Updated 2/13/06 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/J Tg construct: hAPPSwInd Promotor: PDGFB Injected: C57BL/6 x DBA/2F2 embryos C57BL/6 X DBA/2 F1 mice WM spatial memory retention, acquisition, deficits 6-7 months (Palop et al., 2003) Total Aβ, and Aβ42 in neocortical and hippocampus High levels of Aβ(1-42) resulted in age-dependent formation of Aβ plaques in mutant hAPP mice but not wild-type hAPP mice Available The Jackson Lab Stock#:004661 (See JAX datasheet) Mucke et al., 2000 PDGF -APPSwInd line J9 Updated 7/7/04   The Swedish mutation was introduced into the PDGF-APPInd transgene. PDGF-APPSw, Ind transgene injected into (C57BL/6 × DBA/2) F2 one-cell embryos. C57BL/6 x DBA/2 F2 N/A 2-4 month old tg mice had almost twice as much A in their hippocampi, but much lower human APP levels than APPInd (line H6) tg mice. No amyloid plaques were detected yet electrophysiological recordings in hippocampal slice preparations detected synaptic transmission deficits.   Hsia et al., 1999 APP695 Line C3-3 Symbol: App695 Posted 2/12/07 C3B6-Tg(APP695)3Dbo/J B6C3H pronuclei were injected with cDNA encoding a chimeric APP695, with human gene mutations K595N, M596L, regulated by mouse prion promoter. Repository-cryopreserved Congenic mice with APPswe develop memory deficits Mice expressing this transgene develop amyloid deposits in brain tissue by 18-20 months of age. Available The Jackson Lab Stock#: 003375 Borchelt et al., 1996 APP/RK    Alpha Secretion cDNA with K687E, R684D/ mouse thy-1 gene promoter FVB/N neophobic reaction, progressive CNS disorganization, premature death no change in NMDA receptor density or distribution. None of the typical hallmark of AD (Amyloid deposits, neurofibrillary tangles) Unpatented Contact Paul Van Dun. These mice are no longer available. Moechars D et al., 1996  TgAPPSwe-KI   humanized Aβ and introduced the K670N/M671L FAD mutation into a single transgenic line, exon 16. Outbred CD-1 N/A 9 fold greater than in normal human brain and nonamyloidogenic processing is depressed. Spatial and temporal expression patterns of human Aβ are reproduced. Contact: Dorothy Flood or Steve Trusko Reaume et al., 1996 APP751Swedish (APP14) Symbol: APP Updated 1/12/04   APP751 Swedish /Human Thy-1 Origin: C57B6J No abnormal behavior reported 2 fold overexpression of APP mRNA. No indication of AD pathology up to an age of 2 years. Unpatented Contacts: Matthias Staufenbiel Andrä et al., 1996 APP Swe/London (APP22) Symbol: APP Updated 1/12/04   APP Swe/London/Human Thy-1 promoter Origin:C57B/6J   2x over expression of APP mRNA. Diffuse Aβ deposits detected in neocortex and hippocampus at 18 months. Exhibit Neuritic changes, dystrophic cholinergic fibers and hyperphosphorylated tau. Unpatented Contact: Matthias Staufenbiel Sturchler-Pierrat et al., 1997 APP751 Swedish (APP23) Symbol: APP Updated 1o/30/05   APP751Swedish/ murine Thy-1.2 Origin: C57BL/6J Learning impairment in Morris water maze and a passive avoidance paradigm. 7x over expression of APP mRNA. A deposits at 6 months, by 24 months in neocortex and hippocampus. Inflammation, neuritic and synaptic degeneration and tau hyperphosphorylation. Evidence for Cerebral amyloid angiopathy (CAA). Unpatented Contact: Matthias Staufenbiel Sturchler-Pierrat et al., 1997 TgCRND8 Updated 10/30/05   APPSwe/Ind (KM670/671NL+V717F)/ hamster prior promoter Hybrid C3H/He-C57BL/6 At 3 months impairment in acquisition and learning reversal in memory version of the Morris water maze. Immunization against Aβ42 offset learning impairment (Janus). Aβ deposits at 3 months of age, by 10 weeks levels of Aβ40 and Aβ42 peptides 5-fold higher than endogenous Mo-APP. Dense-cored plaques and neuritic pathology evident from 5 months of age. Activated microglia appear concurrently with plaques. Contact: David Westway Chishti, MA et al., 2001 PDAPP(Line109) Symbol:APP Updated 10/30/05   Minigene encoding codon717Valine to Phenylalanine mutation/modified hAPP introns 6,7,8 in construct resulted in expression of 770, 751 and 695 isoforms of human APP/PDGF-β promoter. SwissWebster x B6D2F1 (C57Bl/6 x DBA/2) Significant impairment on a variety of different learningand memory tests Aβ deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis 5,811,633,  5,877,015, Contact: Dora Games or Dale Schenk Games et al., 1995; Rockenstein et al., 1995 hBACE Symbol: APP Posted 3/6/2005   hBACE / MoPrP.Xho /a 15.9-kb NotI linear fragment Origin and background C57B6/C3H. Maintained as homozygous N/A BACE L, M and H express 7, 10 and 20-fold BACE over endogenous levels, respectively. No evidence of Aß deposition. Increased BACE expression in neuronal cell bodies, axons and synaptic elements of the hippocampus, puncta within the granule cell layer of the cerebellum, and neuropil within the spinal cord. Contact: Virginia M-Y Lee vmylee@mail.med.upenn.edu Lee et al., 2005 hBACE54 Symbol: BACE Posted 8/10/04   hBACE cDNA inserted into Xho1 of vector pTSCa1/murine Thy-1 promoter Origin: C57BL/6J; backcross >10 gen No major changes. Detailed analysis not yet performed hBACE mRNA ~ 4x higher than endogenous mRNA. Consistant hBACE protein expression in BACE54/4 line but variation in the Bace54/11 line. Highest protein in the cortex and hippocampus and lowest in the cerebellum. Contact Paolo Paganetti Bodendorf et al., 2002 Bace1 -/- (See JAX datasheet) Symbol: BACE Updated 1/18/05 B6.129-Bacetm1Pcw/J Disrupted 2-kb of BACE 1 containing exon 1 (residues 1-87)/ replaced with a neomycin-resistance gene/transfected into R1 ES cells/ C57BL/6J blastocysts. Origin: C57BL/6 mice; Backcross 7 Gen. Viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product detected in brain tissue. Primary cultures of cortical neurons do not secrete amyloid β peptides (Aβ 1-40/42 or Aβ11-40/42) or beta C-terminal fragments ( CTFs). Available The Jackson Lab: Stock 004714 Cai et al., 2001 BACE1 Null     Normal Healthy, fertile and appear normal in gross anatomy, tissue histology.   Unpatented Luo Y et al