|Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6.Cg-Mapttm1Hnd Tg(MAPT*V337M)1Gds/Mmjax MMRRC Stock Number 036211.|
|The ht-PAC-377M transgenic mouse expresses all 6 human tau isoforms with 3 repeat (3R)-tau as the predominant isoform and 4 repeat (4R) -tau as the second most abundant isoform. Mutations in MAPT are associated with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP 17). Unpublished data suggests that these mice have behavioral deficits and oxidative damage in the brain. This mutant mouse strain may be useful in studies of tau isoforms in neurodegenerative disease.|
Type Congenic; Mutant Strain; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation +pN1
Donating Investigator Gerard Schellenberg, University of Pennsylvania
Homozygotes/Hemizygotes: Mice that are homozygous for the targeted mutation and hemizygous for the transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These double mutant mice produce mutated human tau (MAPT), while no endogenous mouse tau (Mapt) is produced. The ht-PAC-377M transgenic mouse expresses all 6 human tau isoforms with 3 repeat (3R)-tau as the predominant isoform and 4 repeat (4R) -tau as the second most abundant isoform. Mutations in MAPT are associated with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP 17). Unlike several of the other ht-PAC mutations, 377M does not influence exon 10 expression. Unpublished data suggests that these mice have behavioral deficits and oxidative damage in the brain. This mutant mouse strain may be useful in studies of tau isoforms in neurodegenerative disease.
The transgenic construct contains the 201 kb P1 artificial chromosome (PAC) 61D6 and includes 5 kb of sequence upstream of the human MAPT promoter and an additional 62 kb downstream of the 3' end of MAPT. The downstream segment also contains the 3' end of the gene KIAA1267, however, human MAPT is the only complete gene in the PAC. The construct includes the mutation V337M in exon 12 representing a GTG to ATG nucleotide substitution. This mutation results in an amino acid substitution of methionine for valine at position 337. This transgene was microinjected into fertilized C57BL/6 x C3H hybrid oocytes and founder mice were crossed to C57BL/6 mice for 15 generations. Mice were crossed to B6.129-Mapttm1Hnd mice to generate mice that are homozygous for the targeted mutation and hemizygous for the transgene. The colony was maintained by sibling mating. Upon arrival, mice were bred to C57BL/6J mice to establish the colony.
|Considerations for Choosing Controls|
Strains carrying Mapttm1Hnd alleleView Strains carrying Mapttm1Hnd (6 strains)Strains carrying other alleles of MAPT
005491 B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 017326 B6.Cg-Mapttm1Hnd Tg(MAPT)1Gds/Mmjax 015852 B6.Cg-Mapttm1Hnd Tg(MAPT*S305S)4Gds/Mmjax 017459 B6.Cg-Mapttm1Hnd Tg(MAPT*)1Gds/Mmjax 017798 B6.Cg-Mapttm1Hnd Tg(Thy1-MAPT*)3610Gds/Mmjax 008323 B6.Cg-Tg(Mc4r-MAPT/Sapphire)21Rck/J 008321 B6.Cg-Tg(Npy-MAPT/Sapphire)1Rck/J 018923 B6.Cg-Tg(PDGFB-MAPT*P301S)77Elan/J 008324 B6.Cg-Tg(Pmch-MAPT/CFP)1Rck/J 008322 B6.Cg-Tg(Pomc-MAPT/Topaz)1Rck/J 004807 B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax 008169 B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J 003741 B6D2-Tg(Prnp-MAPT)43Vle/J 024841 B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J 015815 FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ 004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 014092 STOCK Tg(ACTB-tTA2,-MAPT/lacZ)1Luo/J 024854 STOCK Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*P301L)#Kha/JView Strains carrying other alleles of MAPT (18 strains)Strains carrying other alleles of Mapt
005491 B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 018282 B6.Cg-Mapttm1(Mecp2)Jae/LimmJ 021162 B6;129P2-Mapttm2Arbr/J 012639 B6;129S4-Mapttm3(HDAC2)Jae/J 004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 004779 STOCK Mapttm1(EGFP)Klt/J 025195 STOCK Tg(Vmn1r191-Mapt/CFP)1Dlc/JView Strains carrying other alleles of Mapt (7 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.Frontotemporal Dementia; FTD (MAPT)
Parkinson Disease, Late-Onset; PD (MAPT)
Parkinson-Dementia Syndrome (MAPT)
Pick Disease of Brain (MAPT)
Supranuclear Palsy, Progressive, 1; PSNP1 (MAPT)
View Research Applications
|Allele Name||targeted mutation 1, Hana N Dawson|
|Allele Type||Targeted (Null/Knockout)|
|Mutation Made By||Michael Vitek, Duke University Medical Center|
|Strain of Origin||129X1/SvJ|
|Gene Symbol and Name||Mapt, microtubule-associated protein tau|
|Gene Common Name(s)||AI413597; AW045860; DDPAC; FTDP-17; MAPTL; MSTD; MTBT1; MTBT2; Mtapt; PPND; PPP1R103; RNPTAU; TAU; Tau; expressed sequence AI413597; expressed sequence AW045860; pTau;|
|Molecular Note||Exon 1, encoding the translational start site, was replaced by a neomycin selection cassette via homologous recombination. RT-PCR analysis of total brain RNA obtained from homozygous mutant mice showed a lack of transcript produced by the targeted locus.The absence of encoded protein was verified by Western blot analysis of brain homogenates as well as by immunocytochemical analysis of coronal sections. [MGI Ref ID J:78649]|
|Allele Name||transgene insertion 1, Gerard Schellenberg|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Strain of Origin||C57BL/6 x C3H|
|Expressed Gene||MAPT, microtubule-associated protein tau, human|
|Promoter||MAPT, microtubule-associated protein tau, human|
|Molecular Note||The transgenic construct contains the 201 kb P1 artificial chromosome (PAC) 61D6 and includes 5 kb of sequence upstream of the human MAPT promoter and an additional 62 kb downstream of the 3' end of MAPT. The downstream segment also contains the 3' end of the gene KIAA1267, however, human MAPT is the only complete gene in the PAC . The construct includes the mutation V337M in exon 12 representing an GTG to ATG nucleotide substitution. This mutation results in an amino acid substitution of methionine for valine at position 337. Line 1 was generated. [MGI Ref ID J:152671]|
McMillan P; Korvatska E; Poorkaj P; Evstafjeva Z; Robinson L; Greenup L; Leverenz J; Schellenberg GD; D'Souza I. 2008. Tau isoform regulation is region- and cell-specific in mouse brain. J Comp Neurol 511(6):788-803. [PubMed: 18925637] [MGI Ref ID J:152671]
Andrews-Zwilling Y; Bien-Ly N; Xu Q; Li G; Bernardo A; Yoon SY; Zwilling D; Yan TX; Chen L; Huang Y. 2010. Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J Neurosci 30(41):13707-17. [PubMed: 20943911] [MGI Ref ID J:165492]
Baglietto-Vargas D; Kitazawa M; Le EJ; Estrada-Hernandez T; Rodriguez-Ortiz CJ; Medeiros R; Green KN; LaFerla FM. 2014. Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition. Neurobiol Dis 62:407-15. [PubMed: 24176788] [MGI Ref ID J:207203]
Dawson HN; Cantillana V; Jansen M; Wang H; Vitek MP; Wilcock DM; Lynch JR; Laskowitz DT. 2010. Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease. Neuroscience 169(1):516-31. [PubMed: 20434528] [MGI Ref ID J:165237]
Dawson HN; Ferreira A; Eyster MV; Ghoshal N; Binder LI; Vitek MP. 2001. Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J Cell Sci 114(Pt 6):1179-87. [PubMed: 11228161] [MGI Ref ID J:78649]
Gomez de Barreda E; Perez M; Gomez Ramos P; de Cristobal J; Martin-Maestro P; Moran A; Dawson HN; Vitek MP; Lucas JJ; Hernandez F; Avila J. 2010. Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits. Neurobiol Dis 37(3):622-9. [PubMed: 20004245] [MGI Ref ID J:158536]
Higuchi M; Ishihara T; Zhang B; Hong M; Andreadis A; Trojanowski J; Lee VM. 2002. Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration. Neuron 35(3):433-46. [PubMed: 12165467] [MGI Ref ID J:78400]
Holth JK; Bomben VC; Reed JG; Inoue T; Younkin L; Younkin SG; Pautler RG; Botas J; Noebels JL. 2013. Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy. J Neurosci 33(4):1651-9. [PubMed: 23345237] [MGI Ref ID J:193896]
Jimenez-Mateos EM; Gonzalez-Billault C; Dawson HN; Vitek MP; Avila J. 2006. Role of MAP1B in axonal retrograde transport of mitochondria. Biochem J 397(1):53-9. [PubMed: 16536727] [MGI Ref ID J:116415]
Jin YN; Chen PC; Watson JA; Walters BJ; Phillips SE; Green K; Schmidt R; Wilson JA; Johnson GV; Roberson ED; Dobrunz LE; Wilson SM. 2012. Usp14 deficiency increases tau phosphorylation without altering tau degradation or causing tau-dependent deficits. PLoS One 7(10):e47884. [PubMed: 23144711] [MGI Ref ID J:192359]
Lei P; Ayton S; Finkelstein DI; Spoerri L; Ciccotosto GD; Wright DK; Wong BX; Adlard PA; Cherny RA; Lam LQ; Roberts BR; Volitakis I; Egan GF; McLean CA; Cappai R; Duce JA; Bush AI. 2012. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med 18(2):291-5. [PubMed: 22286308] [MGI Ref ID J:180272]
Luo Y; Nie YJ; Shi HR; Ni ZF; Wang Q; Wang JZ; Liu GP. 2013. PTPA activates protein phosphatase-2A through reducing its phosphorylation at tyrosine-307 with upregulation of protein tyrosine phosphatase 1B. Biochim Biophys Acta 1833(5):1235-43. [PubMed: 23428800] [MGI Ref ID J:199030]
Meilandt WJ; Yu GQ; Chin J; Roberson ED; Palop JJ; Wu T; Scearce-Levie K; Mucke L. 2008. Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci 28(19):5007-17. [PubMed: 18463254] [MGI Ref ID J:135174]
Morris M; Hamto P; Adame A; Devidze N; Masliah E; Mucke L. 2013. Age-appropriate cognition and subtle dopamine-independent motor deficits in aged tau knockout mice. Neurobiol Aging 34(6):1523-9. [PubMed: 23332171] [MGI Ref ID J:203367]
Nakamura K; Greenwood A; Binder L; Bigio EH; Denial S; Nicholson L; Zhou XZ; Lu KP. 2012. Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease. Cell 149(1):232-44. [PubMed: 22464332] [MGI Ref ID J:186082]
Palop JJ; Chin J; Roberson ED; Wang J; Thwin MT; Bien-Ly N; Yoo J; Ho KO; Yu GQ; Kreitzer A; Finkbeiner S; Noebels JL; Mucke L. 2007. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55(5):697-711. [PubMed: 17785178] [MGI Ref ID J:126808]
Reyes JF; Fu Y; Vana L; Kanaan NM; Binder LI. 2011. Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease. Am J Pathol 178(5):2275-85. [PubMed: 21514440] [MGI Ref ID J:171582]
Roberson ED; Halabisky B; Yoo JW; Yao J; Chin J; Yan F; Wu T; Hamto P; Devidze N; Yu GQ; Palop JJ; Noebels JL; Mucke L. 2011. Amyloid-beta/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J Neurosci 31(2):700-11. [PubMed: 21228179] [MGI Ref ID J:168226]
Roberson ED; Scearce-Levie K; Palop JJ; Yan F; Cheng IH; Wu T; Gerstein H; Yu GQ; Mucke L. 2007. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 316(5825):750-4. [PubMed: 17478722] [MGI Ref ID J:121330]
Seward ME; Swanson E; Norambuena A; Reimann A; Cochran JN; Li R; Roberson ED; Bloom GS. 2013. Amyloid-beta signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease. J Cell Sci 126(Pt 5):1278-86. [PubMed: 23345405] [MGI Ref ID J:200462]
Vossel KA; Zhang K; Brodbeck J; Daub AC; Sharma P; Finkbeiner S; Cui B; Mucke L. 2010. Tau reduction prevents Abeta-induced defects in axonal transport. Science 330(6001):198. [PubMed: 20829454] [MGI Ref ID J:164887]
Yamada K; Cirrito JR; Stewart FR; Jiang H; Finn MB; Holmes BB; Binder LI; Mandelkow EM; Diamond MI; Lee VM; Holtzman DM. 2011. In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J Neurosci 31(37):13110-7. [PubMed: 21917794] [MGI Ref ID J:191549]
Zempel H; Luedtke J; Kumar Y; Biernat J; Dawson H; Mandelkow E; Mandelkow EM. 2013. Amyloid-beta oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. EMBO J 32(22):2920-37. [PubMed: 24065130] [MGI Ref ID J:202831]
de Barreda EG; Dawson HN; Vitek MP; Avila J. 2010. Tau deficiency leads to the upregulation of BAF-57, a protein involved in neuron-specific gene repression. FEBS Lett 584(11):2265-70. [PubMed: 20338169] [MGI Ref ID J:160378]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry While maintaining a live colony, mice homozygous for the Mapttm1Hnd (TAU-) targeted mutation and hemizygous for the Tg(MAPT*V337M)1Gds (hT-PAC-337M) transgene are bred with mice homozygous for the TAU- targeted mutation and wildtype (noncarrier) for the hT-PAC-337M transgene.
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