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| These transgenic mice express the P301S mutant human microtubule-associated protein tau, MAPT, under the direction of the mouse prion protein, Prnp, promoter and may be useful in studies of neurodegenerative tauopathy and Alzheimer's disease. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Noncarrier x Hemizygote (Female x Male) Species laboratory mouse Generation ?+N1F0 (28-JUL-08) Donating Investigator Virginia Lee, University of Pennsylvania Description
These transgenic mice express the P301S mutant human microtubule-associated protein tau, MAPT, under the direction of the mouse prion protein, Prnp, promoter. The expression of the mutant human MAPT is five-fold higher than the expression of the endogenous mouse MAPT protein. Hyperphosphorylated, insoluble mutant human MAPT protein in the brain accumulates with age causing decreased microtubule binding. At three months of age, transgenic mice exhibit clasping and limb retraction when lifted by the tail, which progresses to limb weakness. By 10 months of age the mice exhibit a hunched back and paralysis, followed by inability to feed. Transgenic mice have a median lifespan of approximately nine months with approximately 80% dying by 12 months. Histological analysis reveals neuron degeneration in hippocampus and ventricular dilatation (brain atrophy) by eight months of age, although significant neuron degeneration in the hippocampus occurs at approximately nine months of age. Neuron loss spreads to the amygdala, neocortex and entorhinal cortex by 12 months of age. Defective translocation of endoplasmic reticulum proteins in affected neurons is observed as early as three months of age. The onset of neurofibrillay tangle formation in the neocortex, amygdala, hippocampus, brain stem and spinal cord is five months of age. Transgenic mice display neuroinflammation with microglial activation and astrogliosis. The ultrastructure of the neurofibrillay tangle-like lesions detected is similar to that found in brain lesions of human Alzheimer's disease and tauopathy patients. Degradation of synaptic function is significant by six months of age. These mice cannot be bred to homozygosity, homozygous females do not mate. This mutant mouse strain may be useful in studies of neurodegenerative tauopathy and Alzheimer's disease.Development
A transgenic construct containing the P301S mutant human microtubule-associated protein tau, MAPT, under the direction of the mouse prion protein, Prnp, promoter was injected into fertilized B6C3F1 mouse eggs. Founder animals were bred to B6C3F1/J or B6C3F1/Crl mice. The resulting transgenic mice were maintained as hemizygotes on the B6C3F1 background before arriving at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of MAPT
View Strains carrying other alleles of MAPT (6 strains)
Additional Web Information
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*P301S)PS19Vle/0
involves: C3H * C57BL/6
- life span-post-weaning/aging
- premature death (MGI Ref ID J:119741)
- ~80% of mice die by 12 months of age, with median survival of ~9 months
- behavior/neurological phenotype
- abnormal eating behavior (MGI Ref ID J:119741)
- mice are no longer able to feed after onset of paralysis
- hunched posture (MGI Ref ID J:119741)
- paralysis is associated with hunched-back posture
- limb grasping (MGI Ref ID J:119741)
- at 3 months of age, mice exhibit limb grasping and limb retraction when lifted by the tail, whereas mice expressing a wild-type MAPT transgene show no neurodegenerative phenotype up to 24 months of age
- paralysis (MGI Ref ID J:119741)
- mice show paralysis at 7-10 months of age
- weakness (MGI Ref ID J:119741)
- limb grasping at 3 months of age is followed by limb weakness
- nervous system phenotype
- abnormal CNS synaptic transmission (MGI Ref ID J:119741)
- basal synaptic transmission is impaired at 6 months
- mice show small fiber volley amplitude, fEPSP slopes and amplitudes at all stimulus intensities tested
- abnormal excitatory postsynaptic potential (MGI Ref ID J:119741)
- at 6 months, the maximum fEPSP is reduced relative to wild-type MAPT transgenic mice
- decreased paired-pulse facilitation (MGI Ref ID J:119741)
- at 6 months, mice show significantly reduce paired pulse facilitation (PPF) ratio at all stimulus intervals
- reduced long term potentiation (MGI Ref ID J:119741)
- LTP in CA1 region of hippocampus is significantly deteriorated, indicating attenuated postsynaptic responsiveness and compromised synaptic plasticity, but at 6 months no overt reduction in neuron number is detected
- abnormal brain morphology (MGI Ref ID J:119741)
- limb grasping at 3 months of age is followed by brain atrophy
- abnormal amygdala morphology (MGI Ref ID J:119741)
- neuron loss is observed at 12 months of age
- abnormal brain ventricle morphology (MGI Ref ID J:119741)
- by 8 months of age, ventricular dilatation is seen
- abnormal cerebral cortex morphology (MGI Ref ID J:119741)
- at 3 months, mice have neurofilament light chain and tau-positive spheroids in the cerebral cortex
- prominent atrophy of neocortex is observed at 9 months of age, with a 20% reduction in volume at 12 months of age
- decreased pyramidal neuron number (MGI Ref ID J:119741)
- significant reduction in number is found at 12 months of age, but no loss is detected at 6 months
- abnormal entorhinal cortex morphology (MGI Ref ID J:119741)
- neuron loss is observed at 12 months of age
- abnormal hippocampus morphology (MGI Ref ID J:119741)
- at 9 months of age, there is marked hippocampal atrophy, with ~25% and ~40% reductions in hippocampal volume at 9 and 12 months of age respectively
- abnormal dentate gyrus morphology (MGI Ref ID J:119741)
- at 3 months, mice have neurofilament light chain and tau-positive spheroids in the dentate gyrus, as well as in the cortex
- abnormal hippocampal mossy fiber morphology (MGI Ref ID J:119741)
- at 3 months but not at 6 months, neurofilament light chain-positive mossy fibers are not detected in CA3 of hippocampus at 3 months but not at 6 months, neurofilament light chain-positive mossy fibers are not detected in CA3 of hippocampus
- decreased pyramidal neuron number (MGI Ref ID J:119741)
- significant reduction in number is found at 12 months of age, but no loss is detected at 6 months
- hippocampal neuron degeneration (MGI Ref ID J:119741)
- loss of hippocampal neurons (MGI Ref ID J:119741)
- up to 6 months, mice show no neuron loss, but by 8 months of age, neuron loss in the hippocampus is seen, becoming more severe in hippocampus, as well as amygdala, neocortex and entorhinal cortex by 12 months of age
- neurofibrillary tangles (MGI Ref ID J:119741)
- at 6 months of age, neurofibrillary tangles (NFT) are evident in neocortex, amygdala, hippocampus, brain stem and spinal cord but none are found in mice expressing wild-type human MAPT up to 24 months of age
- tau protein deposits (MGI Ref ID J:119741)
- with aging, brains of mice have increasing levels of insoluble tau deposits composed mainly of transgenic human tau; decrease in solubility of tau is observed between 3 and 6 months
- at 3 months of age, mutants and mice expressing wild-type transgenic human tau show weak perikaryal and dendritic tau staining mainly in hippocampus, amygdala, cortex, brain stem, and spinal cord; at 6 months, mutants show stronger tau-positive neuronal staining in the hippocampus, amygdala, and spinal cord but older mice expressing wild-type human tau protein show no increases up to 12 months
- abnormal spinal cord white matter morphology (MGI Ref ID J:119741)
- at 3 months, mice have neurofilament light chain and tau-positive spheroids in the spinal cord white matter
- astrocytosis (MGI Ref ID J:119741)
- microglial activation precedes astrogliosis in brain regions containing NFTs; this is found in the brain and spinal cord, especially in white matter at 3 months of age with increases seen at 6 months in white and gray matter of hippocampus, amygdala, entorhinal cortex and spinal cord
- gliosis is striking at 6 months in the white matter where little tau pathology exists
- younger mice (3-4 months) show no overt gliosis but increased microglial activation is detected in the hippocampus
- neurodegeneration (MGI Ref ID J:119741)
- mice show progressive neurodegeneration starting at 1 month of age, as determined by increasing loss of synaptophysin immunoreactivity
- muscle phenotype
- dystrophic muscle (MGI Ref ID J:119741)
- affected muscles show group atrophies with small angular fibers, indicating chronic denervation of motor neurons
- progressive muscle weakness (MGI Ref ID J:119741)
- mice show motor increasing weakness and neurogenic muscular atrophy after 3 months of age
Tg(Prnp-MAPT*P301S)PS19Vle/Tg(Prnp-MAPT*P301S)PS19Vle
involves: C3H * C57BL/6
- behavior/neurological phenotype
- abnormal sexual interaction (MGI Ref ID J:119741)
- homozygous females do not mate, so mice have to be maintained as hemizygotes
This mouse can be used to support research in many areas including:
MAPT relatedNeurobiology Research
Alzheimer's Disease
Neurodegeneration
Tg(Prnp-MAPT*P301S)PS19Vle 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*P301S)PS19Vle | ||
|---|---|---|---|
| Allele Name | transgene insertion PS19, Virginia M Y Lee | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | P301S tau (line PS19); PS19 Tg; | ||
| Mutation Made By | Virginia Lee, University of Pennsylvania | ||
| Strain of Origin | (C57BL/6 x C3H)F1 | ||
| Expressed Gene | MAPT, microtubule-associated protein tau, human | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| Molecular Note | The transgene construct contains the P301S mutant human microtubule-associated protein tau, MAPT, under the direction of the mouse prion protein, Prnp, promoter. The expression of the mutant human MAPT is 5-fold higher than the expression of the endogenous mouse Mapt protein. [MGI Ref ID J:119741] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Prnp-MAPT*P301S)PS19Vle, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Yoshiyama Y; Higuchi M; Zhang B; Huang SM; Iwata N; Saido TC; Maeda J; Suhara T; Trojanowski JQ; Lee VM. 2007. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53(3):337-51. [PubMed: 17270732] [MGI Ref ID J:119741]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as hemizygotes. These mice cannot be bred to homozygosity, homozygous females do not mate. Mating System Noncarrier x Hemizygote (Female x Male) 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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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle x Noncarrier $288.65 Noncarrier x Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle x Noncarrier $375.30 Noncarrier x Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | ||
| 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. | ||
General Terms and Conditions
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