Strain Name:

B6.Cg-Mapttm1Hnd Tg(MAPT)1Gds/Mmjax

Availability:

Cryopreserved - Ready for recovery     Available at the JAX MMRRC

Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6.Cg-Mapttm1Hnd Tg(MAPT)1Gds/Mmjax MMRRC Stock Number 036116.
These double mutant (ht-PAC-N) mice produce normal human tau (MAPT), while no endogenous mouse tau (Mapt) is produced. This strain serves as a control for human tau mutations 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.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

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.
Specieslaboratory mouse
Generation?+F1pN1
Generation Definitions
 
Donating Investigator Gerard Schellenberg,   University of Pennsylvania

Description
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 normal human tau (MAPT), while no endogenous mouse tau (Mapt) is produced. The ht-PAC-N transgenic mouse expresses all 6 human tau isoforms by P24 with the 3 repeat (3R)-tau predominant to the 4 repeat (4R) -tau ratio. This strain serves as a control for human tau mutations associated with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP 17). 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.

Development
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 . This transgene was microinjected into fertilized C57BL/6 x C3H hybrid oocytes and founder mice were crossed to C57BL/6 mice for at least 10 generations. Founder line 1 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.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Mapttm1Hnd     (6 strains)

View Strains carrying other alleles of MAPT     (18 strains)

View Strains carrying other alleles of Mapt     (6 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related 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

Research Applications
This mouse can be used to support research in many areas including:

MAPT related

Neurobiology Research
Alzheimer's Disease
Parkinson's Disease

Mapttm1Hnd related

Neurobiology Research
Alzheimer's Disease
      Tau (Mapt) mutants

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mapttm1Hnd
Allele Name targeted mutation 1, Hana N Dawson
Allele Type Targeted (knock-out)
Common Name(s) TAU-;
Mutation Made By Michael Vitek,   Duke University Medical Center
Strain of Origin129X1/SvJ
Gene Symbol and Name Mapt, microtubule-associated protein tau
Chromosome 11
Gene Common Name(s) AI413597; AW045860; DDPAC; FTDP-17; MAPTL; MSTD; MTBT1; MTBT2; Mtapt; PPND; 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 Symbol Tg(MAPT)1Gds
Allele Name transgene insertion 1, Gerard Schellenberg
Allele Type Transgenic (random, expressed)
Common Name(s) hT-PAC-N;
Strain of OriginC57BL/6 x C3H
Expressed Gene MAPT, microtubule-associated protein tau, human
Promoter MAPT, microtubule-associated protein tau, human
Molecular Note The only complete gene in PAC clone 61D6 from Research Genetics is MAPT. This PAC is 201 kb and contains 5 kb sequence upstream of the promoter and an additional 62 kb downstream of the 3' end. [MGI Ref ID J:152671]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MAPT)1Gds, Separated PCR
Mapttm1Hnd, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Mapttm1Hnd related

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]

Barreda EG; Avila J. 2011. Tau regulates the subcellular localization of calmodulin. Biochem Biophys Res Commun 408(3):500-4. [PubMed: 21531208]  [MGI Ref ID J:172402]

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]

Fuster-Matanzo A; de Barreda EG; Dawson HN; Vitek MP; Avila J; Hernandez F. 2009. Function of tau protein in adult newborn neurons. FEBS Lett 583(18):3063-8. [PubMed: 19695252]  [MGI Ref ID J:153129]

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]

Morris M; Koyama A; Masliah E; Mucke L. 2011. Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease. PLoS One 6(12):e29257. [PubMed: 22206005]  [MGI Ref ID J:182343]

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]

Rapoport M; Dawson HN; Binder LI; Vitek MP; Ferreira A. 2002. Tau is essential to beta -amyloid-induced neurotoxicity. Proc Natl Acad Sci U S A 99(9):6364-9. [PubMed: 11959919]  [MGI Ref ID J:125456]

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]

Tg(MAPT)1Gds related

Min SW; Cho SH; Zhou Y; Schroeder S; Haroutunian V; Seeley WW; Huang EJ; Shen Y; Masliah E; Mukherjee C; Meyers D; Cole PA; Ott M; Gan L. 2010. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 67(6):953-66. [PubMed: 20869593]  [MGI Ref ID J:167861]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as homozygous for the targeted mutation and hemizygous for the transgene.

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