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Strain Name:

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

Stock Number:

003741

Availability:

Repository-Cryopreserved


General Terms and Conditions

Former Name      B6SJL-Tg(Prnp-MAPT)43Vle/J    (Changed: 15-DEC-04 )
Genes & Alleles   MAPT;   Prnp;   Tg(Prnp-MAPT)43Vle;


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
GenerationN5+N1p (19-FEB-06)

Strain 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.

Strain 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.

Related Disease (OMIM) Terms

Microtubule-Associated Protein Tau; MAPT
Mammalian Phenotype Terms assigned by genotype

Tg(Prnp-MAPT)43Vle/0

        involves: C57BL/6 * DBA/2
  • nervous system phenotype
  • abnormal axon morphology (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 (J:61052)
    • fast axonal transport of proteins is retarded as compared to wildtype
  • abnormal motor neuron morphology (J:61052)
    • in addition to inclusions, vacuolar lesions are observed in older mice
    • motor neuron degeneration (J:61052)
  • astrocytosis (J:61052)
    • detectable after one month of age
  • axon degeneration (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 (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 (J:61052)
    • impaired ability to stand on slanted surface
  • limb grasping (J:61052)
    • mice retract hindlimbs when lifted by the tail
  • growth/size phenotype
  • decreased body weight (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 (J:61052)
    • mice die in utero or within three months
  • life span-post-weaning/aging
  • premature death (J:61052)
    • mice die in utero or within three months

Gene & Allele Details

Allele Symbol Tg(Prnp-MAPT)43Vle
Allele Name transgene insertion 43, Virginia M Y Lee
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. [J:61052]

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls

Genotyping Protocols

TgN(Mapt)

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

Related Strains

View Strains carrying other alleles of MAPT     (3 strains)

View Strains carrying other alleles of Prnp     (17 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.

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)

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]  [J:61052]

Additional References

Price and Supply Information

Strain Name: B6D2-Tg(Prnp-MAPT)43Vle/J
Stock Number: 003741

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to the 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; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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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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