Overview

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 Unpublished data suggests that these mice have behavioral deficits and oxidative damage in the brain.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.

Donating Investigator

Gerard Schellenberg, University of Pennsylvania

Genetic overview

Genetic Background	Generation

Mapt^tm1Hnd

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Mapt	microtubule-associated protein tau

Tg(MAPT*V337M)1Gds

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

Neurobiology Research

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Details

Detailed 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 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 Unpublished data suggests that these mice have behavioral deficits and oxidative damage in the brain.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.

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. 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-Mapt^tm1Hnd 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.

Expression Data

Expressed Gene	MAPT, microtubule associated protein tau, human
Site of Expression

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):788-803PubMed: 18925637 MGI: J:152671

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Genetics

Mapt^tm1Hnd

Allele Symbol: Mapt^tm1Hnd

Allele Name	targeted mutation 1, Hana N Dawson
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

Tg(MAPT*V337M)1Gds

Allele Symbol: Tg(MAPT*V337M)1Gds

Allele Name	transgene insertion 1, Gerard Schellenberg
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	hT-PAC-337^M
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Mapt^tm1Hnd related

Neurobiology Research
- Alzheimer's Disease
  - Tau (Mapt) mutants

Mammalian Phenotype Terms by Genotype

References

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):788-803PubMed: 18925637 MGI: J:152671

Additional - Mapt^tm1Hnd related

Additional - Tg(MAPT*V337M)1Gds related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:** human MAPT*V337M
- Separated PCR:Tg(MAPT*V337M)1Gds
- Standard PCR:Mapt
- Standard PCR:Mapt
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, mice homozygous for the Mapt^tm1Hnd (TAU^-) targeted mutation and hemizygous for the Tg(MAPT*V337M)1Gds (hT-PAC-337^M) transgene are bred with mice homozygous for the TAU^- targeted mutation and wildtype (noncarrier) for the hT-PAC-337^M transgene.
- Additional Breeding and Husbandry Support
Citation
When using the B6.Cg-Mapt^tm1Hnd 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.

Animal Health Reports

Facility Barrier Level Descriptions

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

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Mapttm1Hnd

Allele Symbol: Mapttm1Hnd

Tg(MAPT*V337M)1Gds

Allele Symbol: Tg(MAPT*V337M)1Gds

Disease Terms

Research Areas By Phenotype

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

Genotype: Mapttm1Hnd related

Mammalian Phenotype Terms by Genotype

References

Additional - Mapttm1Hnd related

Additional - Tg(MAPT*V337M)1Gds related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Mapt^tm1Hnd

Allele Symbol: Mapt^tm1Hnd

Genotype: Mapt^tm1Hnd related

Additional - Mapt^tm1Hnd related