|Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6.Cg-Mapttm1Hnd Tg(MAPT*S305S)4Gds/Mmjax MMRRC Stock Number 034408.|
|These double mutant (ht-PAC-305S) mice produce mutated human tau (MAPT), while no endogenous mouse tau (Mapt) is produced. S305S is associated with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP 17). This mutant mouse strain may be useful in studies of tau isoforms in neurodegenerative disease.|
Former Names B6.Cg-Mapttm1Hnd Tg(MAPT*S305S)4Gds (Changed: 22-SEP-11 ) Type Congenic; 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 N15pN1
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-305S transgenic mouse expresses all 6 human tau isoforms with a 3 repeat (3R)-tau to 4 repeat (4R) -tau ratio of approximately 80% 4R-tau to 20% 3R-tau rather than the expected human ratio of 1:1. S305S is associated with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP 17) and is believed to increase exon 10 inclusion during splicing by strengthening the weak exon 10 5' splice site. No gross or microscopic pathologic lesions were observed in these mice. This mutant mouse strain may be useful in studies of tau isoforms in neurodegenerative disease.
Heterozygote: Not evaluated.
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 "silent" mutation S305S in exon 10 representing an AGT to AGC nucleotide substitution. This mutation does not result in an amino acid substitution. This transgene was microinjected into fertilized C57BL/6 x C3H hybrid oocytes and founder mice were crossed to C57BL/6 mice for 15 generations. Founder line 4 was 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 017459 B6.Cg-Mapttm1Hnd Tg(MAPT*)1Gds/Mmjax 017545 B6.Cg-Mapttm1Hnd Tg(MAPT*V337M)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 025820 B6;CBA-Tg(CRH-MAPT/Topaz)1Rck/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 025104 FVB/N-Tg(tetO/Prnp-MAPT*P301L,-luc)Y74Dbo/J 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 (20 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 ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Tau (Mapt) mutants
Tau (Mapt) mutants
|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 4, Gerard Schellenberg|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Expressed Gene||MAPT, microtubule-associated protein tau, human|
|Promoter||MAPT, microtubule-associated protein tau, human|
|Molecular Note||The transgene contains the complete sequence of human MAPT gene as contained in the P1 artificial chromosome (PAC) 61D6 (Research Genetics, Huntsville, AL). This downstream segment contains the 3 prime end of the gene KIAA1267. MAPT is the only completegene on this PAC. The S305S mutation was introduced into this PAC using a 2- step recombineering process. [MGI Ref ID J:152671]|
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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]
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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]
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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]
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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, these mice are bred as homozygous for the targeted mutation and hemizygous for the transgene.
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