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Strain Name:

B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J

Stock Number:

008169

Availability:

Under Development for Distribution Colony

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Genes & Alleles   MAPT;   Prnp;   Tg(Prnp-MAPT*P301S)PS19Vle;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Virginia Lee,   University of Pennsylvania

Strain 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 5-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 3 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 9 months with approximately 80% dying by 12 months. Histological analysis reveals neuron degeneration in hippocampus and ventricular dilatation (brain atrophy) by 8 months of age, although significant neuron degeneration in the hippocampus occurs at approximately 9 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 3 months of age. The onset of neurofibrillay tangle formation in the neocortex, amygdala, hippocampus, brain stem and spinal cord is 5 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 6 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.

Strain 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.

Mammalian Phenotype Terms assigned by genotype

Tg(Prnp-MAPT*P301S)PS19Vle/0

        involves: C3H * C57BL/6
  • life span-post-weaning/aging
  • premature death (J:119741)
    • ~80% of mice die by 12 months of age, with median survival of ~9 months
  • behavior/neurological phenotype
  • abnormal eating behavior (J:119741)
    • mice are no longer able to feed after onset of paralysis
  • hunched posture (J:119741)
    • paralysis is associated with hunched-back posture
  • limb grasping (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 (J:119741)
    • mice show paralysis at 7-10 months of age
  • weakness (J:119741)
    • limb grasping at 3 months of age is followed by limb weakness
  • nervous system phenotype
  • abnormal CNS synaptic transmission (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 (J:119741)
      • at 6 months, the maximum fEPSP is reduced relative to wild-type MAPT transgenic mice
    • decreased paired-pulse facilitation (J:119741)
      • at 6 months, mice show significantly reduce paired pulse facilitation (PPF) ratio at all stimulus intervals
    • reduced long term potentiation (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 (J:119741)
    • limb grasping at 3 months of age is followed by brain atrophy
    • abnormal amygdala morphology (J:119741)
      • neuron loss is observed at 12 months of age
    • abnormal brain ventricle morphology (J:119741)
      • by 8 months of age, ventricular dilatation is seen
    • abnormal cerebral cortex morphology (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 (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 (J:119741)
      • neuron loss is observed at 12 months of age
    • abnormal hippocampus morphology (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 (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 (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 (J:119741)
        • significant reduction in number is found at 12 months of age, but no loss is detected at 6 months
      • hippocampal neuron degeneration (J:119741)
      • loss of hippocampal neurons (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 (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 (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 (J:119741)
    • at 3 months, mice have neurofilament light chain and tau-positive spheroids in the spinal cord white matter
  • astrocytosis (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 (J:119741)
    • mice show progressive neurodegeneration starting at 1 month of age, as determined by increasing loss of synaptophysin immunoreactivity
  • muscle phenotype
  • dystrophic muscle (J:119741)
    • affected muscles show group atrophies with small angular fibers, indicating chronic denervation of motor neurons
  • progressive muscle weakness (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 (J:119741)
    • homozygous females do not mate, so mice have to be maintained as hemizygotes

Gene & Allele Details

Allele Symbol Tg(Prnp-MAPT*P301S)PS19Vle
Allele Name transgene insertion PS19, Virginia M Y Lee
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. [J:119741]

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as hemizygotes. These mice cannot be bred to homozygosity, homozygous females do not mate.

Related Strains

Strains carrying other alleles of MAPT
005491   B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
003741   B6D2-Tg(Prnp-MAPT)43Vle/J
004808   STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
View Strains carrying other alleles of MAPT     (3 strains)

View Strains carrying other alleles of Prnp     (17 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

MAPT related

Neurobiology Research
Alzheimer's Disease
Parkinson's Disease

Tg(Prnp-MAPT*P301S)PS19Vle related

Neurobiology Research
Alzheimer's Disease (Tau (Mapt) mutants)

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]  [J:119741]

Price and Supply Information

Strain Name: B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J
Stock Number: 008169
 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard SupplyUnder Development for Distribution Colony
Supply Notes This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  

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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.
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