Overview

These double mutant mice produce human tau (MAPT) truncated at amino acid E391 and no endogenous mouse tau (Mapt). The E391 mutant tau exhibits the pathologic phenotype - conformational change or hyperphosphorylation - in the inner dentate molecular layer, CA1 neuronal soma and apical dendrites and cingulate gyrus neuropil. Despite the existence of "pretangle" tau pathology, mice do not develop late-stage neurofibrillary tangles. This mutant mouse strain may be useful in studies of tau 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(Thy1-MAPT*)3610Gds

Allele Type
Transgenic (Inserted expressed sequence)

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Research Applications

Neurobiology Research

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Details

Detailed Description

These double mutant mice produce human tau (MAPT) truncated at amino acid E391 and no endogenous mouse tau (Mapt). The high expressing E391-3610 transgenic mouse expresses the most abundant tau isoform found in the adult human brain, 4R1N, at 2.6 fold higher than normal endogenous mouse tau. Proteolytic cleavage of tau at the C-terminus is associated with neurofibrillary tangles and abnormal neurites in Alzheimer's Disease. The E391 mutant tau exhibits the pathologic phenotype - conformational change or hyperphosphorylation - in the inner dentate molecular layer, CA1 neuronal soma and apical dendrites and cingulate gyrus neuropil. Despite the existence of "pretangle" tau pathology, mice do not develop late-stage neurofibrillary tangles. This mutant mouse strain may be useful in studies of tau in neurodegenerative disease.

Development

The transgenic construct contains the human MAPT (tau) 4R1N isoform truncated at amino acid position E391(glutamic acid) and under the direction of the Thy1^b (Thy1.2) neuron specific promoter. The construct contains sequences encoded by alternatively spliced exons 2 and 10 and has 4 microtubule repeats.
This transgene was microinjected into fertilized C57BL/6 x C3H/HeJ hybrid oocytes. Founder line 3610 was established and crossed to C57BL/6 mice for a minimum of 12 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

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

McMillan PJ; Kraemer BC; Robinson L; Leverenz JB; Raskind M; Schellenberg G. 2011. Truncation of tau at E391 promotes early pathologic changes in transgenic mice. J Neuropathol Exp Neurol 70(11):1006-19PubMed: 22002427 MGI: J:179578

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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(Thy1-MAPT*)3610Gds

Allele Symbol: Tg(Thy1-MAPT*)3610Gds

Allele Name	transgene insertion 3610, Gerard Schellenberg
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	E391-3610; THY1.2::TauE391
Gene Symbol and Name	Tg(Thy1-MAPT*)3610Gds, transgene insertion 3610, Gerard Schellenberg
Gene Synonym(s)
Promoter	Thy1, thymus cell antigen 1, theta, mouse, laboratory
Expressed Gene	MAPT, microtubule associated protein tau, human
Strain of Origin	C57BL/6 x C3H
Chromosome	UN
Molecular Note	The transgenic construct contains the 4R1N tau isoform truncated at amino acid position E391(glutamic acid) and under the direction of the Thy1b (Thy1.2) neuron specific promoter. The construct contains sequences encoded by alternatively spliced exons 2 and 10 and has 4 microtubule repeats. Lines 3608 and 3610 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 PJ; Kraemer BC; Robinson L; Leverenz JB; Raskind M; Schellenberg G. 2011. Truncation of tau at E391 promotes early pathologic changes in transgenic mice. J Neuropathol Exp Neurol 70(11):1006-19PubMed: 22002427 MGI: J:179578

Additional - Mapt^tm1Hnd related

Additional - Tg(Thy1-MAPT*)3610Gds related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Tg(Thy1-MAPT*)3608/3610Gds
- Standard PCR:Mapt
- Standard PCR:Mapt
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygous for the targeted mutation and hemizygous for the transgene.
- Additional Breeding and Husbandry Support
Citation
When using the B6.Cg-Mapt^tm1Hnd Tg(Thy1-MAPT*)3610Gds/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36485 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(Thy1-MAPT*)3610Gds

Allele Symbol: Tg(Thy1-MAPT*)3610Gds

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(Thy1-MAPT*)3610Gds 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