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 Unpublished data suggests that these mice have behavioral deficits and oxidative damage in the brain.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.
Gerard Schellenberg, University of Pennsylvania
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Mapt | microtubule-associated protein tau |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
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 Unpublished data suggests that these mice have behavioral deficits and oxidative damage in the brain.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.
Expressed Gene | MAPT, microtubule associated protein tau, human |
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Site of Expression |
Allele Name | targeted mutation 1, Hana N Dawson |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | MaptKO(Duke); TAU- |
Gene Symbol and Name | Mapt, microtubule-associated protein tau |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 11 |
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. |
Mutations Made By | Michael Vitek, Duke University Medical Center |
Allele Name | transgene insertion 1, Gerard Schellenberg |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hT-PAC-337M |
Gene Symbol and Name | Tg(MAPT*V337M)1Gds, transgene insertion 1, Gerard Schellenberg |
Gene Synonym(s) | |
Promoter | MAPT, microtubule associated protein tau, human |
Expressed Gene | MAPT, microtubule associated protein tau, human |
Strain of Origin | C57BL/6 x C3H |
Chromosome | UN |
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. |
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.
When using the B6.Cg-Mapttm1Hnd Tg(MAPT*V337M)1Gds/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36211 in your Materials and Methods section.
Facility Barrier Level Descriptions
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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