1887

Abstract

Summary

The grey tremor mouse is an autosomal recessive mutant characterized by a phenotype of unusual pigmentation, neurological abnormalities and early death. These mice have a spongiform encephalopathy similar to scrapie and Creutzfeldt-Jakob disease. Although the disease is clearly heritable, the grey tremor mouse spongiform pathology has also been transmitted by inoculation of genetically normal mice with diseased brain homogenates. The possibility that a scrapie-like agent is involved has been proposed. We examined brain homogenates from grey tremor mice, scrapie-affected mice and normal mice for the presence of the mouse scrapie agent protein (MoSp33–37) and its normal cellular homologue. All untreated homogenates contained one or both isoforms of this protein as detected on immunoblots. Grey tremor mouse brain homogenates, when protease-treated, showed no evidence of MoSp33–37. A purification method for MoSp33–37 concentrated it in samples from scrapie-affected mice, but this protein was not detected in grey tremor or normal mice. These results suggest that it is unlikely that the scrapie agent is involved in grey tremor disease.

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1988-04-01
2024-12-13
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References

  1. BARRY R. A., MCKINLEY M. P., BENDHEIM P. E., LEWIS G. K., DEARMOND S. J., PRUSINER S. B. 1985; Antibodies to the scrapie protein decorate prion rods. Journal of Immunology 135:603–613
    [Google Scholar]
  2. BASLER K., OESCH B., SCOTT M., WESTAWAY D., WALCHLI M., GROTH D. F., MCKINLEY M. P., PRUSINER S. B., WEISSMANN C. 1986; Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46:417–428
    [Google Scholar]
  3. BENDHEIM P. E., BOLTON D. C. 1986; A 54-kDa normal cellular protein may be the precursor of the scrapie agent protease-resistant protein. Proceedings of the National Academy of Sciences, U.S.A 83:2214–2218
    [Google Scholar]
  4. BENDHEIM P. E., BARRY R. A., DEARMOND S. J., STITES D. P., PRUSINER S. B. 1984; Antibodies to a scrapie prion protein. Nature, London 310:418–421
    [Google Scholar]
  5. BENDHEIM P. E., BOOKMAN J. M., MCKINLEY M. P., KINGSBURY D. T., PRUSINER S. B. 1985; Scrapie and Creutzfeldt-Jakob disease prion proteins share physical properties and antigenic determinants. Proceedings of the National Academy of Sciences, U.S.A 82:997–1001
    [Google Scholar]
  6. BOOKMAN J. M., PRUSINER S. B., TATEISHI J., KINGSBURY D. T. 1987; Immunoblotting of Creutzfeldt-Jakob disease prion proteins: host species-specific epitopes. Annals of Neurology 21:589–595
    [Google Scholar]
  7. BOLTON D. C, MCKINLEY M. P., PRUSINER S. B. 1982; Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311
    [Google Scholar]
  8. BOLTON D. C, MCKINLEY M. P., PRUSINER S. B. 1984; Molecular characteristics of the major scrapie prion protein. Biochemistry 23:5898–5906
    [Google Scholar]
  9. BOLTON D. C, BENDHEIM P. E., MARMORSTEIN A. D., POTEMPSKA A. 1987; Isolation and structural studies of the intact scrapie agent protein. Archives of Biochemistry and Biophysics 258:579–590
    [Google Scholar]
  10. BROWN P., COKER-VANN M., POMEROY K., FRANKO M., ASHER D. M., GIBBS C. J. JR, GAJDUSEK D. C. 1986; Diagnosis of Creutzfeldt-Jakob disease by Western blot identification of marker protein in human brain tissue. New England Journal of Medicine 314:547–551
    [Google Scholar]
  11. CARLSON G. A., KINGSBURY D. T., GOODMAN P. A., COLEMAN S., MARSHALL S. T., DEARMOND S. I., WESTAWAY D., PRUSINER S. B. 1986; Linkage of prion protein and scrapie incubation time genes. Cell 46:503–511
    [Google Scholar]
  12. CARP R. I., MERZ P. A., KASCSAK R. J., MERZ G. S., WISNIEWSKI H. M. 1985; Nature of the scrapie agent: current status of facts and hypotheses. Journal of General Virology 66:1357–1368
    [Google Scholar]
  13. DIENER T. O. 1987; PrP and the nature of the scrapie agent. Cell 49:719–721
    [Google Scholar]
  14. HOFFMAN P. M., ROHWER R. G., MACAULEY C, BILELLO J. A., HARTLEY J. W., MORSE H. C. 1987; Transmission in NFS/N mice of the heritable spongiform encephalopathy associated with the grey tremor mutation. Proceedings of the National Academy of Sciences, U.S.A 84:3866–3870
    [Google Scholar]
  15. HOPE J., MORTON L. J. D., FARQUHAR C. F., MULTHAUP G., BEYREUTHER K., KIMBERLIN R. H. 1986; The major polypeptide of scrapie-associated fibrils (SAF) has the same size, charge distribution, and N-terminal protein sequence as predicted for the normal brain protein (PrP). EMBO Journal 5:2591–2597
    [Google Scholar]
  16. KASCSAK R. J., RUBENSTEIN R., MERZ P. A., CARP R. I., ROBAKIS N. K., WISNIEWSKI H. M., DIRINGER H. 1986; Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. Journal of Virology 59:676–683
    [Google Scholar]
  17. KINNEY H. C., SIDMAN R. L. 1986; Pathology of the spongiform encephalopathy in the gray tremor mutant mouse. Journal of Neuropathology and Experimental Neurology 45:108–126
    [Google Scholar]
  18. LOCHT C, CHESEBRO B., RACE R., KEITH J. M. 1986; Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent. Proceedings of the National Academy of Sciences, U.S.A 83:6372–6376
    [Google Scholar]
  19. MCKINLEY M. P., BOLTON D. C., PRUSINER S. B. 1983; A protease-resistant protein is a structural component of the scrapie prion. Cell 35:57–62
    [Google Scholar]
  20. MERZ P. A., ROHWER R. G., KASCSAK R., WISNIEWSKI H. M., SOMERVILLE R. A., GIBBS C. I. JR, GAJDUSEK D. C. 1984; Infection-specific particle from the unconventional slow virus diseases. Science 225:437–440
    [Google Scholar]
  21. MEYER R. K., MCKINLEY M. P., BOWMAN K. A., BRAUNFELD M. B., BARRY R. A., PRUSINER S. B. 1986; Separation and properties of cellular and scrapie prion proteins. Proceedings of the National Academy of Sciences, U.S.A 83:2310–2314
    [Google Scholar]
  22. OESCH B., WESTAWAY D., WALCHLI M., MCKINLEY M. P., KENT S. B. H., AEBERSOLD R., BARRY R. A., TEMPST P., TEPLOW D. B., HOOD L. E., PRUSINER S. B., WEISSMANN C. 1985; A cellular gene encodes scrapie PrP27-30 protein. Cell 40:735–746
    [Google Scholar]
  23. ROBAKIS N. K., SAWH P. R., WOLFE G. C, RUBENSTEIN R., CARP R. I., INNIS M. A. 1986; Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues. Proceedings of the National Academy of Sciences, U.S.A 83:6377–6381
    [Google Scholar]
  24. RUBENSTEIN R., MERZ P. A., KASCSAK R. J., CARP R. I., SCALICI C. L., FAMA C. L., WISNIEWSKI H. M. 1987; Detection of scrapie-associated fibrils (SAF) and SAF proteins from scrapie-affected sheep. Journal of Infectious Diseases 156:36–42
    [Google Scholar]
  25. SIDMAN R. L., KINNEY H. C., SWEET H. O. 1985; Transmissible spongiform encephalopathy in the gray tremor mutant mouse. Proceedings of the National Academy of Sciences, U.S.A 82:253–257
    [Google Scholar]
  26. SPARKES R. S., SIMON M., COHEN V. H., FOURNIER R. E. K., LEM J., KLISAK I., HEINZMANN C, BLATT C, LUCERO M., MOHANDAS T., DEARMOND S. J., WESTAWAY D., PRUSINER S. B., WEINER L. P. 1986; Assignment of the human and mouse prion protein genes to homologous chromosomes. Proceedings of the National Academy of Sciences, U.S.A 83:7358–7362
    [Google Scholar]
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