Strain Name:

B6D2-Tg(Prnp-MAPT)43Vle/J

Stock Number:

003741

Availability:

Repository-Cryopreserved

Description

Strain Information

Former Names B6SJL-Tg(Prnp-MAPT)43Vle/J    (Changed: 15-DEC-04 )
Type Mutant Stock; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
GenerationN5+N1p (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
   Noncarrier
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of MAPT     (6 strains)

View Strains carrying other alleles of Prnp     (20 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

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      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/2
  • lethality-prenatal/perinatal
  • *normal* lethality-prenatal/perinatal (MGI Ref ID J:61052)
    • mice die in utero or within three months
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:61052)
    • mice die in utero or within three months
View Research Applications

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

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

MAPT related

Neurobiology Research
Alzheimer's Disease
Parkinson's Disease

Tg(Prnp-MAPT)43Vle related

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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

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 related

Lim 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

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen 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 View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
Cryopreserved Embryos Fee $1600.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
Cryopreserved Embryos Fee $2080.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryopreserved Embryos
    This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • 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
 
  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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Contact Information
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Fax: 207.288.6150
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Terms of Use

Terms of Use


General Terms and Conditions


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fax:207-288-6655

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