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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
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Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 11-JUL-08 Species laboratory mouse Generation ?+N1F9 (01-JUL-11)
Generation DefinitionsDonating 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
Alzheimer's Disease Models
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Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
assigned by genotype
Tg(Prnp-MAPT*P301S)PS19Vle/0
involves: C3H * C57BL/6
- mortality/aging
- premature death
- ~80% of mice die by 12 months of age, with median survival of ~9 months (MGI Ref ID J:119741)
- behavior/neurological phenotype
- abnormal eating behavior
- mice are no longer able to feed after onset of paralysis (MGI Ref ID J:119741)
- hunched posture
- paralysis is associated with hunched-back posture (MGI Ref ID J:119741)
- limb grasping
- 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 (MGI Ref ID J:119741)
- paralysis
- mice show paralysis at 7-10 months of age (MGI Ref ID J:119741)
- weakness
- limb grasping at 3 months of age is followed by limb weakness (MGI Ref ID J:119741)
- nervous system phenotype
- abnormal CNS synaptic transmission
- abnormal excitatory postsynaptic potential
- at 6 months, the maximum fEPSP is reduced relative to wild-type MAPT transgenic mice (MGI Ref ID J:119741)
- reduced long term potentiation
- 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 (MGI Ref ID J:119741)
- abnormal brain morphology
- limb grasping at 3 months of age is followed by brain atrophy (MGI Ref ID J:119741)
- abnormal amygdala morphology
- neuron loss is observed at 12 months of age (MGI Ref ID J:119741)
- abnormal brain ventricle morphology
- by 8 months of age, ventricular dilatation is seen (MGI Ref ID J:119741)
- abnormal cerebral cortex morphology
- abnormal entorhinal cortex morphology
- neuron loss is observed at 12 months of age (MGI Ref ID J:119741)
- abnormal hippocampus morphology
- 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 (MGI Ref ID J:119741)
- abnormal dentate gyrus morphology
- at 3 months, mice have neurofilament light chain and tau-positive spheroids in the dentate gyrus, as well as in the cortex (MGI Ref ID J:119741)
- abnormal hippocampal mossy fiber morphology
- 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 (MGI Ref ID J:119741)
- abnormal hippocampus pyramidal cell morphology
- significant reduction in number in the hippocampal CA3 region is found at 12 months of age, but no loss is detected at 6 months (MGI Ref ID J:119741)
- hippocampal neuron degeneration (MGI Ref ID J:119741)
- loss of hippocampal neurons
- 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 (MGI Ref ID J:119741)
- neurofibrillary tangles
- 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 (MGI Ref ID J:119741)
- tau protein deposits
- 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 (MGI Ref ID J:119741)
- 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 (MGI Ref ID J:119741)
- abnormal spinal cord white matter morphology
- at 3 months, mice have neurofilament light chain and tau-positive spheroids in the spinal cord white matter (MGI Ref ID J:119741)
- astrocytosis
- 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 (MGI Ref ID J:119741)
- gliosis is striking at 6 months in the white matter where little tau pathology exists (MGI Ref ID J:119741)
- younger mice (3-4 months) show no overt gliosis but increased microglial activation is detected in the hippocampus (MGI Ref ID J:119741)
- decreased paired-pulse facilitation
- at 6 months, mice show significantly reduce paired pulse facilitation (PPF) ratio at all stimulus intervals (MGI Ref ID J:119741)
- neurodegeneration
- mice show progressive neurodegeneration starting at 1 month of age, as determined by increasing loss of synaptophysin immunoreactivity (MGI Ref ID J:119741)
- muscle phenotype
- dystrophic muscle
- affected muscles show group atrophies with small angular fibers, indicating chronic denervation of motor neurons (MGI Ref ID J:119741)
- progressive muscle weakness
- mice show motor increasing weakness and neurogenic muscular atrophy after 3 months of age (MGI Ref ID J:119741)
Tg(Prnp-MAPT*P301S)PS19Vle/Tg(Prnp-MAPT*P301S)PS19Vle
involves: C3H * C57BL/6
- behavior/neurological phenotype
- abnormal sexual interaction
- homozygous females do not mate, so mice have to be maintained as hemizygotes (MGI Ref ID J:119741)
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 provided by MGI
| 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, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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]
Additional References
Tg(Prnp-MAPT*P301S)PS19Vle relatedCarroll JC; Iba M; Bangasser DA; Valentino RJ; James MJ; Brunden KR; Lee VM; Trojanowski JQ. 2011. Chronic Stress Exacerbates Tau Pathology, Neurodegeneration, and Cognitive Performance through a Corticotropin-Releasing Factor Receptor-Dependent Mechanism in a Transgenic Mouse Model of Tauopathy. J Neurosci 31(40):14436-49. [PubMed: 21976528] [MGI Ref ID J:177434]
Dumont M; Stack C; Elipenahli C; Jainuddin S; Gerges M; Starkova NN; Yang L; Starkov AA; Beal F. 2011. Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. FASEB J 25(11):4063-72. [PubMed: 21825035] [MGI Ref ID J:178410]
Hurtado DE; Molina-Porcel L; Iba M; Aboagye AK; Paul SM; Trojanowski JQ; Lee VM. 2010. A{beta} accelerates the spatiotemporal progression of tau pathology and augments tau amyloidosis in an Alzheimer mouse model. Am J Pathol 177(4):1977-88. [PubMed: 20802182] [MGI Ref ID J:165441]
Ji B; Maeda J; Sawada M; Ono M; Okauchi T; Inaji M; Zhang MR; Suzuki K; Ando K; Staufenbiel M; Trojanowski JQ; Lee VM; Higuchi M; Suhara T. 2008. Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer's and other CNS pathologies. J Neurosci 28(47):12255-67. [PubMed: 19020019] [MGI Ref ID J:142367]
Maeda J; Zhang MR; Okauchi T; Ji B; Ono M; Hattori S; Kumata K; Iwata N; Saido TC; Trojanowski JQ; Lee VM; Staufenbiel M; Tomiyama T; Mori H; Fukumura T; Suhara T; Higuchi M. 2011. In Vivo Positron Emission Tomographic Imaging of Glial Responses to Amyloid-{beta} and Tau Pathologies in Mouse Models of Alzheimer's Disease and Related Disorders. J Neurosci 31(12):4720-4730. [PubMed: 21430171] [MGI Ref ID J:170310]
Min SW; Cho SH; Zhou Y; Schroeder S; Haroutunian V; Seeley WW; Huang EJ; Shen Y; Masliah E; Mukherjee C; Meyers D; Cole PA; Ott M; Gan L. 2010. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 67(6):953-66. [PubMed: 20869593] [MGI Ref ID J:167861]
Takeuchi H; Iba M; Inoue H; Higuchi M; Takao K; Tsukita K; Karatsu Y; Iwamoto Y; Miyakawa T; Suhara T; Trojanowski JQ; Lee VM; Takahashi R. 2011. P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating. PLoS One 6(6):e21050. [PubMed: 21698260] [MGI Ref ID J:174441]
Yata K; Oikawa S; Sasaki R; Shindo A; Yang R; Murata M; Kanamaru K; Tomimoto H. 2011. Astrocytic neuroprotection through induction of cytoprotective molecules; a proteomic analysis of mutant P301S tau-transgenic mouse. Brain Res 1410:12-23. [PubMed: 21803337] [MGI Ref ID J:175758]
Yoshiyama Y; Kojima A; Itoh K; Uchiyama T; Arai K. 2012. Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model. Neurobiol Dis 45(1):329-36. [PubMed: 21889983] [MGI Ref ID J:179843]
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) 11-JUL-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $261.00 Female or Male Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle
Pairs /Price (US dollars $) Pair Genotype $321.00 Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle x Noncarrier $321.00 Noncarrier x Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $339.30 Female or Male Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle
Pairs /Price (US dollars $) Pair Genotype $417.30 Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle x Noncarrier $417.30 Noncarrier x Hemizygous for Tg(Prnp-MAPT*P301S)PS19Vle Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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