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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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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
Former Names B6SJL-Tg(Prnp-MAPT)43Vle/J (Changed: 15-DEC-04 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N6p (19-FEB-06) Donating Investigator Virginia Lee, University of Pennsylvania Description
These transgenic mice express the human fetal tau MAPT isoform under the direction of the mouse prion protein promoter. Hyperphosphorylated, insoluble MAPT protein is widely expressed in neurons of the CNS at levels approximately ten-fold higher than the endogenous mouse counterpart. Mice homozygous for the transgenic insert die at about three months of age. In the hemizygous mice intraneural inclusions that stain positive with T14, a monoclonal antibody specific for MAPT, are observed in brain and spinal cord tissue at 1 month of age. The number of inclusions increases until 6-9 months of age. Transmission electron microscopy studies of these inclusions reveals tightly packed aggregates of randomly arranged 10-20 nm straight filaments. Mice suffer progressive, age-dependant neuronal damage, motor weakness and gliosis. These mice recapitulate key features of tauopathies and provide a model for studying the underlying mechanism of related diseases such as FTDP-17, Alzheimer's and Pick's disease.Development
A transgenic construct containing the mouse Prnp (prion protein) promoter and a cDNA sequence to human MAPT (fetal tau, Tau44 isoform) was used to create transgenic animals on a B6D2F1 background. These mice were crossed with B6SJLF1 mice and then crossed with B6D2F1 mice.
Control Information
| Control | ||
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| Noncarrier | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of MAPT
View Strains carrying other alleles of MAPT (8 strains)
Additional Web Information
Genetic Quality Control Annual Report
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
assigned by genotype
Tg(Prnp-MAPT)43Vle/0
involves: C57BL/6 * DBA/2
- nervous system phenotype
- abnormal axon morphology (MGI Ref ID J:61052)
- spinal cord ventral root contains irregularly shaped axons
- by 12 months of age endoneurial space in ventral root axons appears to increase
- abnormal axonal transport (MGI Ref ID J:61052)
- fast axonal transport of proteins is retarded as compared to wildtype
- abnormal motor neuron morphology (MGI Ref ID J:61052)
- in addition to inclusions, vacuolar lesions are observed in older mice
- motor neuron degeneration (MGI Ref ID J:61052)
- astrocytosis (MGI Ref ID J:61052)
- detectable after one month of age
- axon degeneration (MGI Ref ID J:61052)
- 20% decrease in number of ventral root axons by 12 months of age
- significant reduction in microtubule density by 12 months of age, although neurofilament density is unchanged
- tau protein deposits (MGI Ref ID J:61052)
- tau-positive spheroidal inclusions in spinal cord neurons are visible by 1 month of age
- size and number increases up to 6-9 months of age, but decreases in number by 12 months of age
- inclusions are the size of medium to large spinal cord neurons and some appear to arise within the proximal axons of spinal cord neurons
- spinal cord inclusions are most frequent at the grey-white matter junction
- spinal cord inclusions in line 43 are larger and more abundant than in line 7
- tau-positive inclusions appear in cortical neurons and brainstem by 6 months of age
- inclusions in cortical neurons occur in proximal axons or somadendritic domains of neurons
- inclusions are visible in pontine neurons by 1 month of age
- tau deposits become increasingly insoluble with age
- behavior/neurological phenotype
- impaired balance (MGI Ref ID J:61052)
- impaired ability to stand on slanted surface
- limb grasping (MGI Ref ID J:61052)
- mice retract hindlimbs when lifted by the tail
- growth/size phenotype
- decreased body weight (MGI Ref ID J:61052)
- mice weigh 30-40% less than normal littermates
Tg(Prnp-MAPT)43Vle/Tg(Prnp-MAPT)43Vle
involves: C57BL/6 * DBA/2This mouse can be used to support research in many areas including:
MAPT relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Tg(Prnp-MAPT)43Vle relatedNeurobiology Research
Alzheimer's Disease
Parkinson's Disease
Neurobiology Research
Alzheimer's Disease
Tau (Mapt) mutants
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Prnp-MAPT)43Vle | ||
|---|---|---|---|
| Allele Name | transgene insertion 43, Virginia M Y Lee | ||
| Allele Type | Transgenic (random, expressed) | ||
| Mutation Made By | Virginia Lee, University of Pennsylvania | ||
| Strain of Origin | (C57BL/6 x SJL)F1 | ||
| Expressed Gene | MAPT, microtubule-associated protein tau, human | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| General Note | Three founder lines were generated - lines 7, 27 and 43. Hemizygous mice from line 27 are not viable beyond 3 months and were not characterized in J:61052. Hemizygous mice from line 7 are phenotypically similar to line 43, however inclusions in the spinal cord are smaller and less abundant than in line 43. | ||
| Molecular Note | A transgenic construct containing a cDNA sequence to human MAPT (fetal tau, Tau44 isoform) under the control of the mouse Prnp promtoer was used to create transgenic animals. Quantitative Western blot analysis showed hyperphosphorylated, insoluble MAPT protein to be widely expressed in neurons of the CNS at levels approximately 10 fold higher than the endogenous mouse counterpart. [MGI Ref ID J:61052] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Prnp-MAPT)43Vle, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Ishihara T; Hong M; Zhang B; Nakagawa Y; Lee MK; Trojanowski JQ; Lee VM. 1999. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24(3):751-62. [PubMed: 10595524] [MGI Ref ID J:61052]
Additional References
Nakashima H; Ishihara T; Yokota O; Terada S; Trojanowski JQ; Lee VM; Kuroda S. 2004. Effects of alpha-tocopherol on an animal model of tauopathies. Free Radic Biol Med 37(2):176-86. [PubMed: 15203189] [MGI Ref ID J:90946]
Tg(Prnp-MAPT)43Vle relatedLim J; Balastik M; Lee TH; Nakamura K; Liou YC; Sun A; Finn G; Pastorino L; Lee VM; Lu KP. 2008. Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy. J Clin Invest 118(5):1877-89. [PubMed: 18431510] [MGI Ref ID J:135144]
Nakashima H; Ishihara T; Yokota O; Terada S; Trojanowski JQ; Lee VM; Kuroda S. 2004. Effects of alpha-tocopherol on an animal model of tauopathies. Free Radic Biol Med 37(2):176-86. [PubMed: 15203189] [MGI Ref ID J:90946]
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
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as as hemizygotes. Homozygous mice die at about 3 months of age. It is uncertain if homozygous males can reproduce before death. Coat color expected from breeding: Albino, Agouti, Black. Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 Cryopreserved Embryos $1600.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
| Pricing for International shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 Cryopreserved Embryos $2080.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
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Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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See Terms of Use tab for General Terms and Conditions
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.Ordering and Purchasing Information
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