Dysmyelination in Transgenic Mice Containing the Early Region of JC Virus

  • B. D. Trapp
  • J. A. Small
  • G. A. Scangos


JC virus is a human papovavirus that has been implicated as the causative agent in the chronic human demyelinating disease progressive multifocal leukoencephalopathy (PML). Although the virus is widespread in human populations1, 2, PML in a rare opportunistic disease that occurs primarily in patients with compromised immune systems3. The incidence of PML has increased recently in association with HIV infection4. Numerous studies have shown viral particles within abnormal oligodendrocytes from PML brains5 and the aetiology of demyelination is thought to be due to lytic destruction of these myelin-forming cells. Astrocytes can have bizarre morphologies in PML brains that include some features of transformed cells. Virions are rarely found in electron micrographs of these morphologically altered cells5.


Transgenic Mouse Myelin Basic Protein Progressive Multi Focal Leukoencephalopathy Myelin Sheath Early Region 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gardner, S. D. (1973). Prevalence in England of antibody to human polyomavirus (BK). Br. Med. J., 1, 77–8PubMedCrossRefGoogle Scholar
  2. 2.
    Padgett, B. L. and Walker, D. L. (1973). Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J. Infect. Dis., 127, 467–70PubMedCrossRefGoogle Scholar
  3. 3.
    Johnson, R. T. (1983). Evidence for polyomaviruses in human neurological diseases. In Sever, J. L. and Madden, D. L. (eds.) Polyomaviruses and Human Neurological Disease. pp. 183–90. ( New York: Alan R. Liss )Google Scholar
  4. 4.
    Levy, R. M., Bredesen, D. E. and Rosenblum, M. L. (1985). Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at UCSF and review of the literature. J. Neurosurg., 62, 475–95PubMedCrossRefGoogle Scholar
  5. 5.
    ZuRhein, G. M. (1972). Virions in progressive multifocal leukoencephalopathy. In Minkler, J. (ed.) Pathology of the Nervous System. Vol. 3, pp. 2893–912. ( New York: McGraw-Hill )Google Scholar
  6. 6.
    Walker, D. L., Padgett, B. L., ZuRhein, G. M., Albert, A. E. and Marsh, R. F. (1973). Human papovavirus (JC): induction of brain tumors in hamsters. Science, 181, 674–6PubMedCrossRefGoogle Scholar
  7. 7.
    Padgett, B. L., Walker, D. L., ZuRhein, G. M. and Verakis, J. N. (1977). Differential neuro-oncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters. Cancer Res., 37, 718–20PubMedGoogle Scholar
  8. 8.
    Varakis, J., ZuRhein, G. M., Padgett, B. L. and Walker, D. L. (1978). Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, human polyoma virus. Cancer Res., 38, 1718–22PubMedGoogle Scholar
  9. 9.
    London, W. T., Houff, S. A., Madden, D. L., Fuccillo, D. A., Gravell, M., Wallen, W. C., Palmer, A. E., Sever, J. L., Padgett, B. L., Walker, D. L., ZuRhein, G. M. and Ohashi, T. (1978). Brain tumors in owl monkeys inoculated with a human polyoma virus (JC virus). Science, 102, 1246–9CrossRefGoogle Scholar
  10. 10.
    Tooze, J. (1981). The Molecular Biology of Tumor Viruses. ( Cold Spring Harbor: Cold Spring Harbor Laboratory Press )Google Scholar
  11. 11.
    Small, J. A., Scangos, G. A., Cork, L., Jay, G. and Khoury, G. (1986). The early region of human papovavirus JC induces dysmyelination in transgenic mice. Cell, 46, 13–18PubMedCrossRefGoogle Scholar
  12. 12.
    Gordon, J. W. and Ruddle, F. H. (1983). Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. Methods Enzymol., 101, 411–33PubMedCrossRefGoogle Scholar
  13. 13.
    Small, J. A., Khoury, G., Jay, G., Hawley, P. M. and Scangos, G. A. (1986). Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice. Proc. Natl. Acad. Sci. USA, 83, 8288–92PubMedCrossRefGoogle Scholar
  14. 14.
    Trapp, B. D., Itoyama, Y., Maclntosh, T. D. and Quarles, R. H. (1983). P2 protein in oligodendrocytes and myelin of the rabbit central nervous system. J. Neurochem, 40, 47–54PubMedCrossRefGoogle Scholar
  15. 15.
    Trapp, B. D., Moench, T., Pulley, M., Barbosa, E., Tennekoon, G. and Griffin, J. (1987). Spatial segregation of mRNA encoding myelin-specific proteins. Proc. Natl. Acad. Sci. USA, 84, 7773–7PubMedCrossRefGoogle Scholar
  16. 16.
    Trapp, B. D., Small, J. A., Pulley, M., Khoury, G. and Scangos, G. A. (1988). Dysmyelinadon in transgenic mice containing JC virus early region. Ann. Neurol., 23, 38–48PubMedCrossRefGoogle Scholar
  17. 17.
    Kenney, S., Natarajan, V., Strike, D., Khoury, G. and Salzman, N. P. (1984). JC virus enhancer-promoter active in human brain cells. Science, 226, 1337–9PubMedCrossRefGoogle Scholar
  18. 18.
    Lees, M. B. and Brostaff, S. W. (1984). Proteins of myelin. In Morell, P. (ed.) Myelin. 2nd edn., pp. 197–224. ( New York: Plenum Press )Google Scholar
  19. 19.
    Quarles, R. H. (1983/1984). Myelin-associated glycoprotein in development and disease. Dev. Neurosci., 6, 285–303CrossRefGoogle Scholar
  20. 20.
    Eng, L. F. (1980). The ghat fibrillary acidic (GFA) protein. In Bradshaw, R. A. and Schneider, D. (eds.) Proteins of the Nervous System. pp. 85–117. ( New York: Raven Press )Google Scholar
  21. 21.
    Hogan, E. L. and Greenfield, S. (1982). Animal models of genetic disorders of myelin. In Morell, P. (ed.) Myelin. 2nd edn., pp. 489–534. ( New York: Plenum Press )Google Scholar
  22. 22.
    DePamphilis, M. L. and Wassarman, P. M. (1982). Organization and replication of papovavirus DNA. In Kaplan, A. S. (ed.) Organization and Replication of Viral DNA. pp. 37–114. ( Boca Raton: CRS Press Inc. )Google Scholar
  23. 23.
    Rigby, P. W. J. and Land, P. D. (1983). Structure and function of Simian virus-40 large T-antigen. Adv. Virol. Oncol., 3, 31–47Google Scholar
  24. 24.
    Huber, B., Vakalopaulou, E., Burger, C. and Fanning, E. (1985). Identification and biochemical analysis of DNA replication-defective large T-antigens from SV40-transformed cells. Virology, 146, 188–202PubMedCrossRefGoogle Scholar
  25. 25.
    Cole, C. N., Tornow, J., Clark, R. and Tjian, R. (1986). Properties of the simian virus 40 (SV40) large T-antigens encoded by SV40 mutants with deletions in gene A. J. Virol., 57, 539–46PubMedGoogle Scholar
  26. 26.
    Stahl, H., Droge, P. and Knippers, R. (1986). DNA helicase activity of SV40 large tumor antigen. EMBO J., 5, 1939–44PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • B. D. Trapp
  • J. A. Small
  • G. A. Scangos

There are no affiliations available

Personalised recommendations