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.
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) |
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 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.
The transgenic construct contains the human MAPT (tau) 4R1N 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.
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-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 3610, Gerard Schellenberg |
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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. |
While maintaining a live colony, these mice are bred as homozygous for the targeted mutation and hemizygous for the transgene.
When using the B6.Cg-Mapttm1Hnd 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.
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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