Updated 17 January 2007

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Name/Symbol Strain Name Transgene/ Promoter and Regulatory Elements Genetic Background Behavioral  Phenotype Neurological  Characteristics Patents/ Availability Primary Citation rTg(tauP301L) 4510 Symbol: Tau Posted 12/10/05   Mice expressing activator transgenes tet-off ORF downsteam of Ca2+ calmodulin kinase II promoter/Mice expressing responder transgene, TRE upstream of 4R0N tauP301L mutation. Origin: Activator transgene mice on 129S6, backcross 5x. Responder transgene mice (Tau P301L) on FVB/N. Spatial defects, cognitive impairments early. At 9.5 months exhibit decreased ambulation, body wt, hunched posture but continue to live, now >20 months. Progressive age-related NFTs, and neuronal loss and severe forebrain atrophy. Tau mRNA restricted to forebrain (neuronal cell types). With doxycycline treatment, memory function recovered, neuron numbers stabilized, but NFTs continued to accumulate. Contact Dr. Susan Stoddard Mayo Medical Ventures, Rochester, MN SantaCruz et al., 2005 Tet/GSK3β/Tauvlw Symbol: GSK3β/Tau Posted 10/30/2005   Crossed Tet/GSK3β with Tauvlw/CamKIIa and Thy1.2 Origin: C57Bl6j x CBA Mice are viable and fertile Mice show tau hyperphosphorylation in hippocampal neurons, with thioflavin-S staining and formation of >10nm filaments. Atrophy seen in Tet/GSK-3β mice develops faster in these Tet/ GSK-3β/Tauvlw mice. European Patent Application No 01936609.5. Title, Model for neurodegenerative disease; Inventors: JJ Lucas, F Hernandez, J Avila; Contact Jesús Avila or Felix Hernandez Engel et al., 2005 Tet/GSK3β Symbol: GSK3β Updated 1/25/2006   Tet/GSK-3ß mice were generated by crossing mice expressing tTA under control of the CamKIIa promoter (tTA) with mice that have incorporated the BitetO construct in their genome (TetO). The double transgenic progeny (Tet/GSK-3ß) express GSK-3β constitutively in the brain. Origin: CBAxC57BL/6 Mice are viable and fertile Overexpression of GSK-3β results in neurodegeneration such as β-catenin destabilization and pretangle-like somatodendritic localization of hyperphosphorylated tau. Highest level of transgenic GSK-3β expression is in the hippocampus, then cortex. European Patent Application No 01936609.5. Title, Model for neurodegenerative disease; Inventors: JJ Lucas, F Hernandez, J Avila; Contact Jesús Avila Lucas et al., 2001 APPswe/Tauvlw Symbol: APP/Tau Posted 10/30/2005   Crossed APPSwe (Tg2576) and Tauvlw Origin: C57Bl6j x CBA x SJL At 16 months single APPSwe and double tg mice have increased spatial memory impairment compared to single Tauvlw Double tg mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain areas. European Patent Application No 01936609.5. Title, Model for neurodegenerative disease; Inventors: JJ Lucas, F Hernandez, J Avila; Contact Jesús Avila Perez et al., 2005 GSK3βS9A/Tau4R Symbol: GSK3βS9A/Tau Posted 8/27/2005   Crossed GSK3βS9A with Tau4R Origin: FVB/N (Crl)   Expression in neurons, high level in cortex and hippocampus. Hyperphosphorylation of tau at 4-6 weeks, no insoluble tau aggregates or tangles. Rescue of tau axonopathy of tau 4R. Contact Paul Van Dun Spittaels et al., 2000 APPLo/PS1A246E Symbol: APP/PS1 Posted 7/26/2005   Crossed APPV717I (London) with PS1A246E Origin: FVB/N (Crl)   Both transgenes co-expressed in neurons only. Mice at 6-9 months have increased Aβ levels with amyloid plaques and CAA. Contact Paul Van Dun Dewachter et al., 2000 APPLo/PS1(n-/-) Symbol: APP/PS1 Posted 7/26/2005   Crossed APP(London) with PS1 (n-/-). Origin: FVB/N (Crl)   In bigenic mice the neuronal absence of PS1 effectively prevented amyloid pathology, even in mice that were 18 months old. LTP also was rescued in bigenic mice but not the cognitive defect of APP(V717I) mice. Contact Paul Van Dun Dewachter et al., 2002 BACE x APP(V717I) Symbol: BACE/APP Posted 6/10/2005   Crossed BACE-1 (Line 16) (Willem) with APP(V717I)/mutation hBACE and APP London/mouse Thy 1 Origin: Offspring are double tg that are heterozygous for both transgenes and with identical FVB/C57BL background.   Amyloidogenic processing is increased at Asp1 and Glu11 resulting in more Aβ peptides in bigenic brains. In older bigenic mice BACE1 increased the number of diffuse and senile amyloid plaques. Vascular amyloid deposition was reduced compared single APPV717I mice. Contact Paul Van Dun Willem et al., 2004 APP/ADAM10 OE Symbol: APP/ADAM Posted 6/10/2005   APPV717I were intercrossed with ADAM10 Origin: FVB/N Improved Morris Water Maze test compared to APPV717I mice. Bigenic mice showed increased secretion of the neurotrophic soluble α-secretase-released N-terminal APP domain (APPsα), reduced formation of Aβ peptides, and prevented their deposition in plaques. Functionally, impaired long-term potentiation and cognitive deficits were alleviated. Not available. Contact Falk Fahrenholz Fax 49-6131-392-5348 Postina et al., 2004 APP/ADAM10 dn (catalytically inactive mutant) Symbol: APP/ADAM Posted 6/10/2005   APPV717I were intercrossed with ADAM10 dn Origin: FVB/N Improved Morris Water Maze test compared to APPV717I mice. Expression of ADAM10dn led to an enhancement of the number and size of amyloid plaques in the brains of double-transgenic mice. Not available. Contact Falk Fahrenholz Fax 49-6131-392-5348 Postina et al., 2004 PS2N141I/APPSwe Symbol: PS2-APP Posted 6/9/2005   Crossed male APPSwe (AD147.71H) with female PS2N141I (Prp-huPS2.30H). Murine prion protein genomic fragment (pPrnpHG) was used for PS2 and mThy-1.2 for APPSwe Origin: C57BL/6 x DBA/2. Behavioral changes begin when Aβ deposits and inflammation appear in the subiculum and frontolateral cortex. At 8 months, age-related cognitive deficits and amyloid deposits with inflammation in neo-and limbic cortices. Metabolic profile at 20 months indicates hypometabolism. Contact: Laurence Ozmen Laurence.ozmen@roche.com Richards et al., 2003 APP/RAGE Symbol: RAGE Posted 4/1/2005   hRAGE (see Yan wt hRAGE) crossed with mAPPSwInd (see TJL #004661) C57BL/6J, generation >N10   Earlier abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings than in single tg mice. Contact: Shi Du Yan, sdy1@columbia.edu Arancio et al., 2004 APP/DN-RAGE Symbol: RAGE Posted 4/1/2005   Full-length dominate negative hRAGE /PDGF-ß promoter/6apc1 vector/microinjected into B6CBAF1/J oocytes/ crossed with mAPP (see TJL #004661) C57BL/6J, generation >N10 Normal reproduction and performance Tg APP/dnRAGE animals displayed preservation of spatial learning/memory and diminished neuropathologic changes. Contact: Shi Du Yan, sdy1@columbia.edu Arancio et al., 2004 APPSw/hBACE Symbol: APP/BACE Posted 3/6/2005   Crossed APPSw(KM670/671NL)(Tac #001349) and hBACE (Lee) Bigenic mice C57BL/6/C3H/SJL N/A High BACE overexpression inhibited amyloid formation despite increased β-cleavage of APP, and shifted the subcellular location of APP cleavage to the neuronal perikarya early in the secretory pathway thereby depleting APP destined for axonal transport. Contact: Virginia M-Y Lee vmylee@mail.med.upenn.edu Lee et al., 2005 APP751SL/PS1 KI Symbol:APP/PS1 Updated 5/22/2005   PS1(M233T) (L235P) and APP751 London (V717I), Swedish (K670N/M671L)/Thy1 Origin: C57BL/6 Viable and fertile animals Mice show acceleration of Aβ peptide deposition and develop age-dependent massive neuronal loss in hippocampus (CA1/2 subfield). Strong Aβ immunostaining and accumulation of thioflavine-S-positive stain in pyramidal cell layer precede neuronal loss. Strong astrogliosis occurrs near Aβ-positive neurons. Laurent Pradier Casas et al., 2004 cPS1 conditional Double Ko (cDKo) Symbol: PS1 Posted 7/10/04   Crossed floxed PS1 (fPS1), αCaMKII-Cre transgenic mice and PS2-/- mice together to obtain fPS1/fPS1;αCaMKII-Cre;PS2-/- mice. Origin: C57BL6/129 hybrid Viable, no difference from controls. No alterations in behavior, motor coordination or exploratory anxiety. Mice lacking both presenilins in forebrain exhibit impairments in memory and synaptic plasticity. With age they develop neurodegeneration of cerebral cortex and worsening memory and synaptic function with an increase in p25 and hyperphosphorylated tau. Contact Jie Shen jshen@rics.bwh.harvard.edu Saura et al., 2004 MAPT Mapt EGFP (See JAX datasheet) Updated 1/17/06 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J Double mutant mice were generated by crossing hTau transgenic mice (mouse line 8C) with Mapt targeted mutant mice (Mapt exon disrupted, replaced with EGFP fused to the first 31 MAPT aa. Targeted allele = J1 ES cell then C57BL/6 blastocysts, homozygous. Transgenic allele= Swiss Webster/ B6D2F1, hemizygous; Gen F8 (01-Dec-06) Mice are viable and fertile. No endogenous mouse Tau, six isoforms of hTau expressed. Hyperphosphorylated tau detected in cell bodies and dendrites. Paired helical filaments of aggregated insoluble Tau isolated from brain at 2 months. Available The Jackson Lab: Stock #004808 Use of mice by companies or for-profit entities required a license prior to shipping Andorfer et al., 2003 MAPT Mapt EGFP (See JAX datasheet) Posted 1/17/06 B6.Cg Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J Crossed tg mice (line 8C) with Mapt Targeted mutant mice #004779. Generation N9+1F2 (01-DEC-06) congenic Homozygous for the targeted allele and hemizygous for the transgene. Viable and fertile. No endogenous mouse Tau, six isoforms of hTau expressed. Hyperphosphorylated tau detected in cell bodies and dendrites. Paired helical filaments of aggregated insoluble Tau isolated from brain at 2 months. Available The Jackson Lab: Stock #005491 Use of mice by companies or for-profit entities required a license prior to shipping Andorfer et al., 2003 PS-1(P264L)/APPswe Symbol: PS-1/APP Posted 1/23/04   PS-1 (P264L) mice cross-bred with APP695Swe (Tg2576) or APPsweKI     Cultured neurons have increased Aβ42 and reduced Aβ40. PS-1 mutation increases Aβ42 levels and accelerates amyloid deposits and gliosis. Contact Dorothy Flood at dflood@cephalon.com or Steve Trusko strusko@cephalon.com at Cephalon Siman et al., 2000. APPswe PS1(A246E) Symbol: APP695; Psen1 (See JAX datasheet) Updated 1/18/05 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J Psen-1 tg: hPsen-1 (A246E substitution) (line N-5)/Prnp/B6C3H pronuclei. APP tg: StrainC3B6-Tg(APP695)3Dbo (TJL 003375). Psen-1(A246E) crossed with APPSwe = double trangenic Origin:B6;C3H. Mated double transgenics to C3B6F1 mice. Mice are hemizygous (only 1 in 4 pups is a double transgenic).   Elevated levels of the A 1-42(43) peptide detected in mouse brain homogenates. By 9 months of age, numerous amyloid deposits detected and they increase dramatically between the ages of 10 and 12 months. Available The Jackson Lab: Stock 003378 Borchelt et al, 1997 Mo/Hu APPswe PS1dE9 Symbol: APP695; PSEN1; (See JAX datasheet) Updated 10/1/2005 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J B6C3HF2 pronuclei coinjected with hPsen-1 and APP695/MoPrnp B6C3F1/J background. Cross tg +/+ sibling to Hemizygote. BackcrossG1 Exhibit selective spatial deficit in Morris WM and disinhibitory tendencies in elevated plus maze (Lalond et al., Neurosci Lett 2005) Develop β-amyloid deposits in the brains of transgenic animals by 6 to 7 months of age. APP and PSEN1 are immunodetected in whole brain protein homogenates. Available The Jackson Lab: Stock 004462 Jankowsky et al, 2001 3-Repeat Tau + PSI M146L   Tg expressing 3-repeat human tau isoform, without the N-terminal insert, under the control of a modified promoter of the 3-hydroxy-methyl-glutaryl coenzyme. PS1Tg generated using human mutated PS1M146L under the control of the same promoter. Doubly transgenic mice for human tau and human mutated PS1M146L were generated by cross-breeding of single transgenic mice.     Increased expression of the PS1 holoprotein was observed. Proteolytic fragments of PS1 did not appear to be modified. A somatodendritic accumulation of the transgenic tau and an increase in tau phosphorylation in both tau- and tau/PS1 Tgs. Neurofibrillary tangles were not observed in animals analyzed up to 17 months. Contact J.P. Brion jpbrion@ulb.ac.be Boutajangout et al. Neuroscience Letters 318 (2002) 29–33 APPSwe 2576/Tau JNPL3 Symbol: APP/Tau (See Taconic datasheet) Updated 7/9/04 STOCK-Tg(APPSWE)2576Kha-Tg(MAPT)JNPL3Hlmc P301L 4 repeat Tau (JNPL3) x Appswe (Tg2576) Origin: Crossed homozygous female Tau (Tac #2508M) with hemizygous male APP2576 (Tac #1349T). Developed motor disturbances similar to JNPL3, with identical range in age of onset, including progressive hindlimb weakness, hunched posture, eye irritations, reduced vocalization, and decreased grooming. Developed Aβ deposits at the same age as Tg2576; exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. Available Taconic: Stock #2469 TT (hemizygous for both APP and Tau); #2469WT (wildtype for APP, hemizygous for Tau) Lewis et al., 2001. APPV717/ ApoE-/-     (Swiss Webster X C57BL/6 X DBA/2) X C57BL/6   fibrillar Ab deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APPV717F TG mice.   Holtzman APP + Alpha Synuclein   Heterozygous hSYN mice from line D were crossed with heterozygous hAPP mice from line J9         Masliah et al, 2001