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Model Characteristics - Model:
JCV T-antigen Tg
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| Model Descriptor |
JCV T-antigen Tg
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| Official Nomenclature |
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
C56BL/6J x SJL mixed
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| Is This a Tool Strain? |
No
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Developmental Stage
(applies only to Zebrafish) |
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| Experimental Design |
Transgenic mice were generated using a 3.2 kb Bal1/NciI fragment from the plasmid, pBJC, containing the JCV Mad-4 early promoter sequence and the coding region for the viral early genes. The DNA was microinjected into the pronucleus of fertilized mouse oocytes generated by mating of C57BL/6J ´ SJL mice by DNX Chrysalis. Founder animals were mated with C57BL/6J mice and all mice were screened for the presence of the transgene by DNA extraction from tail tissue and PCR analysis with primers specific to the transgene.
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| Phenotype |
The human polyomavirus, JC virus, has recently been associated with several human CNS tumors, including medulloblastomas and a broad range of glial-origin tumors. This ubiquitous virus is the causative agent of the rare demyelinating disease, progressive multifocal leukoencephalopathy in immunocompromised individuals. Expression of the viral protein, T-antigen, which possesses the ability to transform cells of neural origin, has been detected in human CNS tumors. In an effort to further understand the transforming potential of JCV T-antigen, transgenic mice expressing JCV T-antigen under the control of the Mad-4 promoter were generated. As described previously, approximately 50% of the animals developed pituitary tumors by 1 year of age. However, a small subset of the animals developed solid masses arising from the soft tissues surrounding the salivary gland, the sciatic nerve, and along the extremities that histologically resemble malignant peripheral nerve sheath tumors, rare neoplasms that occur in individuals with neurofibromatosis type 1 (NF1). JCV T-antigen was detected in tumor tissue by immunohistochemistry and immunoprecipitation/Western blotting, but not in normal tissues and was colocalized with NF2, the putative tumor suppressor protein associated with neurofibromatosis type 2, in the nucleus of some cells. In addition, T-antigen was co-precipitated with NF2, but not with NF1 protein, although NF1 was detectable in tumor tissue. Furthermore, precipitated immunocomplexes contained T-antigen, NF2, and p53, suggesting that these three proteins may form a ternary complex. The importance of these findings on mechanisms of T-antigen-mediated tumorigenesis and the pathogenesis of neurofibromatosis are discussed.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
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| Submitted by |
Gordon, Jennifer
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| Principal Investigator / Lab |
Gordon, Jennifer
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| Comment |
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| Model Availability: This model is available from |
| Strain |
Distributor |
Stock number |
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