Updated 22 February 2007

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Name/ Symbol Strain Name Transgene/ Promoter and Regulatory Elements Genetic Background Behavioral  Phenotype Neurological  Characteristics Patents/  Availability Primary Citation Thy-Tau22 Symbol: Tau Posted 02/22/07   Human tau 1N2R with tau mutations G272V and P301S/ Thy 1.2 promotor. Origin: C57Bl/6 No motor deficit until more than 2 years. Memory deficits; neurofibrillary tangles, PHF, and ptau (MC1, AT100, pS422, 12E8, PHF/AD2, AT8, AT180, AT270. Pathology starting in hippocampus. Contact Luc Buee; available for academic research but not for private companies. Schindowski et al., 2006 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 Tau4R-P301L Symbol: Tau Posted 6/10/05   Human Tau-P301L in the Tau-4R/2N isoform/ mouse Thy 1 promoter/injected pronuclear FVB/N embryos Origin: FVB/N Clasping, impaired; Rotarod, normal; Beam walk, failed >9 months; Mean life span, <12 months. Expression level, similar to Tau-4R/2N; Axonal dilations, absent; Intra-neuronal tau aggregates (NFT) , progressive > 6 months, severe at 9-12 months Contact Paul Vandun Terwel et al., 2005 Tau-4R-KOKI Symbol: Tau Posted 6/10/05   Human Tau-4R/2N with no mouse endogenous tau/mouse Thy1 promoter/electroporation ES cells Origin: FVB/N Backcrossed N8 Rotarod, slight impairment > 6 months; Clasping, normal; Beam, slight impairment > 6 months; Mean life span: normal Expression level, similar to endogenous mouse tau with all isoforms combined. Axonal dilations, absent. Tau aggregates, absent. Contact Paul Vandun Terwel et al., 2005 Tau R406W Symbol: Tau Posted 3/6/05   Longest human Tau/R406W mutation/MoPrP.Xho/model of human FTDP-17 Origin B6C3, Line 37 maintained as homozygous Hind leg weaknesses in older mice Mutation promotes the formation of tau lesions with advancing age in neuronal perikarya by novel mechanism initiated by induced impairment of MT binding. This leads to retardation in the slow axonal transport of tau, followed by a cascade of events that culminate in the fibrillization of tau and the formation of NFTs. Contact Virginia M.-Y.Lee Zhang et al., 2004 Human wt Tau Symbol: Tau Posted 3/6/05   human WT tau mutation /MoPrP.Xho/maintain as homozygous Origin: B6C3; Lines 1 and 23 studied 90% survive to 24 months hTau expression is 8-10 times higher than endogenous tau in line 23. No age-dependent accumulation of tau aggregates, no neurodegeneration. Contact Virginia M.-Y.Lee Zhang et al., 2004 Tau Tα1-3RT Symbol: Tau Posted 3/3/05   Minigene of h3RT in pKS vector embedded into modified exons 1-4 in shortest Tau cDNA/ mouse tubulin Tα1 promoter cloned into pcDNA3 vector/ SalI/PvuII fragment of minigene ligated into Tα-1 promoter vector to make Tα1-3RT construct. B6SJL, maintain as heterozygous Mice developed progressive motor weakness in hind and forelimbs. By 24 months of age, limb twitch was observed in 72% of tg mice, compared with 18% of wt mice. Progressive accumulations of tau in astrocytes and oligodendrocytes associated with degeneration of these cells and disruption of myelin sheaths. Aged mice showed numerous glial tau inclusions that were similar to the glial tau pathologies in FTDs. Contact Virginia M.-Y.Lee Higuchi et al., 2002 Tauvlw Symbol: Tau Updated 1/25/06   Linked mutations G272V, P301L, and R406W/site directed mutagenesis hCNS tau cDNA/Mouse Thy-1 promoter with deleted lymphoid enhancer. Origin C57Bl6J x CBA, Backcross to C57Bl/6J 10 generations.   Mice overexpress human mutant Tau in cortex and hippocampus, minimally in spinal cord. Pretangle appearance in neurons expressing mutant tau with filaments of tau and lysosomes having aberrant morphology. Contact J. Avila javila@cbm.uam.es Lim et al., 2001 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 Use of mice by companies or for-profit entities required a license prior to shipping MAPT Mapt EGFP (See JAX datasheet) Posted 1/17/06 B6.CgMapttm1(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 Mapt EGFP (See Jax Datasheet) Symbol: EGFP Updated 1/17/06 STOCK Mapttm1(EGFP)Klt/J cDNA for the enhanced green fluorescent protein (EGFP) was inserted into exon one of tau Mtapt/J1 EScells/C57Bl/6 Origin: mixed background of C57BL/6 and 129/SvJae Viable and fertile. No gross abnormalities in central or peripheral nervous system. GFP seen in neuronal cell bodies and cranial ganglia persists throughout life. Available The Jackson Lab #004779 Tucker et al., 2001 Tau Ko Symbol: Tau Posted 12/19/04 Mapttm1Hnd Replaced exon 1 of mouse tau gene with neo resistant cassette/endogenous promoter. Origin: C57BL/6 x 129SvJ hybrids. Backcross C57BL/6 Gen N8 Breed normally. No expression of Tau protein. Embryonic hippocampal cultures show delay in maturation and are resistant to AB treatment. Human tau proteins can rescue tau-deficient mouse neurons. Contact Hana Dawson dawso009@mc.duke.edu Dawson et al., 2001 T-N279K Symbol: Tau Posted 12/19/04   Minigene of hCNS exons and intronic sequences surrounding exons 2, 3 and 10/ N279K mutation/hTau promoter. C57BL/6 x SJL hybrids Cognitive impairment on radial arm water maze at 52 weeks. Some mice develop motor deficits leading to hind limb paralysis and early demise. Numerous abnormal tau and phospho-tau reactive neurons and glia. Expression of hTau at same level as endogenous. Mice exhibit pathology similar to patients with mutation ie.tau positive tufted astrocytes. Contact Hana Dawson dawso009@mc.duke.edu Unpublished T-WT Symbol: Tau Posted 12/19/04   Minigene of the human CNS expressed exons and intronic sequences surrounding exons 2, 3 and 10/Human Tau promoter C57BL/6 x SJL hybrids Breed normally. Normal behavior No neuropathology. Molecularly, tau isoforms with and without exon 10 are expressed at a 1:1 ratio. Protein expression is ~ 3 times the level of endogenous mouse tau protein. Contact Hana Dawson dawso009@mc.duke.edu Unpublished human Tau Symbol: Tau Posted 12/18/04   PAC 24i13 containing the entire human TAU gene (~200 kBp)/human tau promoter. Origin:C57BL/6 x SJL hybrids. Backcross C57BL/6 Gen N8 Hemizygous mice breed normally; homozygous mice have low level of pregnancies and smaller litters. Increased immunoreactivity to most tau antibodies with some somatodendritic relocalization. No tau aggregates. Contact Hana Dawson dawso009@mc.duke.edu Dawson et al., 2001 C-N279K Symbol: Tau Posted 12/18/04   Minigene of hCNS exons and intronic sequences surrounding exons 2, 3 and 10/ N279K mutation/CMV promoter Origin: C57BL/6 x SJL hybrids Normal. Molecularly, tau isoforms are expressed almost exclusively with exon 10 in adult mice as seen in patients with the mutation. Contact Hana Dawson dawso009@mc.duke.edu Unpublished Tau P301L-JNPL3 (See Taconic datasheet) Symbol:Tau Updated 7/14/04 Stock Tg(MAPT)JNPL3Hlmc Tau P301L/mouse prion promoter/microinjected C57BL/6 x DBA2 X SW fertilized eggs. SW/B6D2F1, line maintained by mating of homozygous mice. Behavioral and motor disturbances related to development of NFT. Phenotype mimics human tauopathies in a more rapid timeframe than the hemizygous model. Taconic Available: Stock #002508-M (homozygous) Lewis J et al Tau P301L-JNPL3 (See Taconic datasheet) Symbol:Tau P301L Updated 7/14/04 Tg(MAPT)JNPL3Hlmc Longest human Tau isoform with 4 repeats containing exon 10 and lacking exons 2 and 3 with P301L/ mouse prion promoter (MoPrP) C57BL/DBA2/SW Severe motor and behavioral disturbances observed early hTau level equal to endogenous tau in hemizygous mice, but 2x the level in homozygous mice. NFT and neuronal loss in brain and spinal cord Unpatented Taconic Available 001638T (hemizygous) 001638W (wildtype) Lewis J et al Tau P301L Line: pR5-182 Updated 3/3/04   Human tau40 isoform with 4 repeats, exons 2 and 3 with P301L/ neuron-specific mouse Thy1.2 promoter. STOCK (mixed C57BL/6, DBA/2, SW). Signs of Wallerian degeneration, neurogenic muscle atrophy,  muscle weakness. Numerous abnormal, tau-reactive nerve cell bodies and dendrites; large numbers of pathologically enlarged axons containing neurofilament and tau-reactive spheroids. Neuronal lesions similar to FTDP-17. Unpatented Contact Jurgen Gotz goetz@bli.unizh.ch   Gotz J et al Tau R406W Updated 11/4/03   Human longest tau cDNA with R406W mutation containing myc and FLAG tags at N- and C- terminal ends, respectively/αCaMk-II promoter B6SJL/F1 backcrossing with C57BL/6J Impaired associative memory in contextual and cued fear conditioning test. Abnormality in prepulse inhibition and forced swim test. No overt sensorimotor deficit. Accumulation of insoluble tau in aged mice. Congophilic hyperphosphorylated tau inclusions only in forebrain neurons of aged mice. Unpatented Contact: Akihiko Takashima Tatebayashi et al. Tau G272V   Human tau40 with G272V mutation/ murine prion protein promoter B6D2F1 x B6D2F1 founder mice inter-crossed with C57BL/6 mice No neurological deficits readily noticeable Filaments in murine oligodendrocytes, associated with tau phosphorylation at AT8 epitope 202/205 in vivo. In the spinal cord, fibrillary inclusions identified by thioflavin-S in oligodendrocytes and motor neurons Unpatented Contact Jurgen Gotz goetz@bli.unizh.ch   Gotz J et al Tau V337M Updated 11/4/03   Human longest tau cDNA with V337M mutation/PDGF-b promoter, neuron-specific mouse Thy1.2 promoter B6SJL background Higher overall spontaneous locomotion. No significant difference in a Morris water maze test. Significant difference in elevated plus maze test and conditional fear test. Neurons of irregular shape in hippocampus were immunoreactive for paired helical filament-associated tau, and showed signs of atrophic cell death disappeared microtubules. Patented Contact Akihiko Takashima Tanemura et al. T44 (3 repeats) Symbol: MAPT Updated 10/30/05 B6D2-Tg(Prnp-MAPT)43Vle/J Shortest human Tau isoform with 3 repeats, wildtype/ Murine Prion Protein, MoPrP.Xho expression vector at XhoI site B6D2/F1 Progressive motor weakness, impaired ability to stand on a slanted surface Accumulation of insoluble tau, profound astrocytosis and axonal degeneration Available (See Jax Datasheet:#003741 Ishihara T et al Tau4R/2N Updated 1/27/05   Longest human Tau isoform with 4 repeats, wildtype/mouse thy-1 cassette, The thymus specific regulatory elements in intron 3 are thereby deleted, making the resulting promoter "neuron-specific" FVB/N Unable to spread hindlimbs when lifted by the tail. Motor disturbances. Axonal degeneration in brain and spinal cord, astrogliosis and ubiquitination in accumulated proteins of dilated axons. Unpatented Contact Paul Vandun Spittaels K et al Tau 4-Repeats-Alz17 Updated 1/28/05   Longest human Tau isoform with 4 repeats, wildtype/mouse Thy.1.2 promoter B6D2F1 x B6D2F1, founder animals were intercrossed with C57BL/6 mice to establish lines Unable to spread hindlimbs when lifted by the tail.  Significant defect in motor coordination. Prominent somatodendritic staining for hyperphosphorylated tau, and pominent axonopathy Unpatented Contact M. Goedert   Probst A et al PP2A Cα mutant L199P Symbol: PP2A Line: Dom1 Updated 3/3/04   cDNA of the human PP2A Ca mutant L199P was isolated from yeast plasmid YEpDE2.5.12 that carries HAPP2ACa-2512 mutant allele/neuron-specific murine Thy1.2 expression vector. Normal size and fertility. Pronuclear microinjection of B6D2F1 x B6D2F1 embryos. Founder animals were intercrossed with C57BL/6 mice to establish lines. N/A High levels of Cα L199P in cortical, hippocampal, and cerebellar neurons. Reduced PP2A activity in brain. Hyperphosphorylation of endogenous tau protein; tau aggregates in cortical pyramidal cells and cerebellar Purkinje cells and co-localized with ubiquitin. Contact Jurgen Gotz Kins, et al., 2001