1887

Abstract

Mouse lines which are congenic for , the major gene controlling scrapie incubation period, have been produced by selective breeding from the inbred C57BL( ) and VM( ) strains; the s7 allele of has been introduced into a VM background by 18 serial backcrosses, at each generation selecting on the basis of the incubation period with the ME7 scrapie strain. The characteristics of the disease produced by seven scrapie strains have been compared in and congenic mice and in the F cross between them. As previously found in non-congenic mice, each scrapie strain has a characteristic, precisely reproducible incubation period pattern in the three genotypes. The gene controls the incubation period for all scrapie strains tested but the direction of allelic action and the apparent dominance pattern differs between scrapie strains. Comparison with non-congenic mice shows that other genes also have a minor effect on incubation period. The distribution of vacuolar degeneration in the brain depends mainly on the scrapie strain but is also influenced by and other unspecified mouse genes. Restriction fragment length polymorphism analysis has already shown that the close linkage between and the gene encoding PrP has been maintained in the congenic lines, strengthening the possibility that PrP is the gene product. The present study confirms that scrapie strains carry information which is independent of the host but nevertheless suggests that host PrP protein interacts with this information to regulate the progression of the disease.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-72-3-595
1991-03-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/72/3/JV0720030595.html?itemId=/content/journal/jgv/10.1099/0022-1317-72-3-595&mimeType=html&fmt=ahah

References

  1. Bazan J. F., Fletterick R. J., McKinley M. P., Prusiner S. B. 1987; Predicted secondary structure and membrane topology of the prion protein. Protein Engineering 1:125–135
    [Google Scholar]
  2. Bolton D. C., Bendheim P. E. 1988; A modified host protein model of scrapie. In Novel Infectious Agents and the Central Nervous System Ciba Foundation Symposium 135 pp 164–181 Edited by Bock G., Marsh J. Chichester: John Wiley;
    [Google Scholar]
  3. Bolton D. C., McKinley M. P., Prusiner S. B. 1982; Identification of a protein that purifies with the scrapie agent. Science 218:1309–1311
    [Google Scholar]
  4. Bruce M. E., Dickinson A. G. 1985; Genetic control of amyloid plaque production and incubation period in scrapie-infected mice. Journal of Neuropathology and Experimental Neurology 44:285–294
    [Google Scholar]
  5. Bruce M. E., Dickinson A. G. 1987; Biological evidence that scrapie agent has an independent genome. Journal of General Virology 68:79–89
    [Google Scholar]
  6. Bruce M. E., Dickinson A. G., Fraser H. 1976; Cerebral amyloidosis in scrapie in the mouse: effect of agent strain and mouse genotype. Neuropathology and Applied Neurobiology 2:471–478
    [Google Scholar]
  7. Bruce M. E., McBride P. A., Farquhar C. F. 1989; Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie. Neuroscience letters 102:1–6
    [Google Scholar]
  8. Carlson G. A., Kingsbury D. T., Goodman P. A., Coleman S., Marshall S. T., DeArmond S., Westaway D., Prusiner S. B. 1986; Linkage of prion protein and scrapie incubation time genes. Cell 46:503–511
    [Google Scholar]
  9. Carlson G. A., Goodman P. A., Lovett M., Taylor B. A., Marshall S. T., Peterson-Torchia M., Westaway D., Prusiner S. B. 1988; Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Molecular and Cellular Biology 8:5528–5540
    [Google Scholar]
  10. Carp R. I., Callahan S. 1986; Scrapie incubation periods and end-point titers in mouse strains differing at the H-2D locus. Intervirology 26:85–92
    [Google Scholar]
  11. Carp R. I., Callahan S. M., Sersen E. A., Moretz R. C. 1984; Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination. Intervirology 21:61–69
    [Google Scholar]
  12. Carp R. I., Moretz R. C., Natelli M., Dickinson A. G. 1987; Genetic control of scrapie: incubation period and plaque formation in I mice. Journal of General Virology 68:401–407
    [Google Scholar]
  13. DeArmond S. J., Mobley W. C., DeMott D. L., Barry R. A., Beckstead J. H., Prusiner S. B. 1987; Changes in the localization of brain prion proteins during scrapie infection. Neurology 37:1271–1281
    [Google Scholar]
  14. Dickinson A. G. 1976; Scrapie in sheep and goats. In Slow Virus Diseases of Animals and Man pp 209–241 Edited by Kimberlin R. H. Amsterdam: North-Holland;
    [Google Scholar]
  15. Dickinson A. G., Fraser H. 1977; Scrapie pathogenesis in inbred mice: an assessment of host control and response involving many strains of agent. In Slow Virus Infections of the Central Nervous System pp 3–14 Edited by ter Meulen V., Katz M. New York: Springer-Verlag;
    [Google Scholar]
  16. Dickinson A. G., Fraser H. 1979; An assessment of the genetics of scrapie in sheep and mice. In Slow Transmissible Diseases of the Nervous System vol 1 pp 367–385 Edited by Prusiner S. B., Hadlow W. J. New York: Academic Press;
    [Google Scholar]
  17. Dickinson A. G., Mackay J. M. K. 1964; Genetical control of the incubation period in mice of the neurological disease, scrapie. Heredity 19:279–288
    [Google Scholar]
  18. Dickinson A. G., Meikle V. M. H. 1971; Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Molecular and General Genetics 112:73–79
    [Google Scholar]
  19. Dickinson A. G., Outram G. W. 1979; The scrapie replication-site hypothesis and its implications for pathogenesis. In Slow Transmissible Diseases of the Nervous System vol 2 pp 13–31 Edited by Prusiner S. B., Hadlow W. J. New York: Academic Press;
    [Google Scholar]
  20. Dickinson A. G., Outram G. W. 1983; Operational limitations in the characterisation of the infective units of scrapie. In Virus Nonconventionnels et Affections du Système Nerveux Central pp 3–16 Edited by Court L. A., Cathala F. Paris: Masson;
    [Google Scholar]
  21. Dickinson A. G., Outram G. W. 1988; Genetic aspects of unconventional virus infections: the basis of the virino hypothesis. In Novel Infectious Agents and the Central Nervous System, Ciba Foundation Symposium 135 pp 63–83 Edited by Bock G., Marsh J. Chichester: John Wiley;
    [Google Scholar]
  22. Dickinson A. G., Meikle V. M. H., Fraser H. 1968; Identification of a gene which controls the incubation period of some strains of scrapie in mice. Journal of Comparative Pathology 78:293–299
    [Google Scholar]
  23. Dickinson A. G., Outram G. W., Taylor D. M., Foster J. D. 1986; Further evidence that scrapie agent has an independent genome. In Unconventional Virus Diseases of the Central Nervous System pp 446–460 Edited by Court L. A., Dormont D., Brown P., Kingsbury D. T. Fontenay-aux-Roses: Commissariat a l’Energie Atomique;
    [Google Scholar]
  24. Diringer H., Gelderblom H., Hilmert H., Ozel M., Elder-bluth C., Kimberlin R. H. 1983; Scrapie infectivity, fibrils and low molecular weight protein. Nature, London 306:476–478
    [Google Scholar]
  25. Doh-ura K., Tateishi J., Kitamoto T., Sasaki H., Sakaki Y. 1990; Creutzfeldt-Jakob disease patients with congophilic kuru plaques have the missense variant prion protein common to Gerstmann-Sträussler syndrome. Annals of Neurology 27:121–126
    [Google Scholar]
  26. Foster J. D., Dickinson A. G. 1988; The unusual properties of CHI641, a sheep-passaged isolate of scrapie. Veterinary Record 123:5–8
    [Google Scholar]
  27. Fraser H. 1976; The pathology of natural and experimental scrapie. In Slow Virus Diseases of Animals and Man pp 267–305 Edited by Kimberlin R. H. Amsterdam: North-Holland;
    [Google Scholar]
  28. Fraser H., Dickinson A. G. 1968; The sequential development of the brain lesions of scrapie in three strains of mice. Journal of Comparative Pathology 78:301–311
    [Google Scholar]
  29. Fraser H., Dickinson A. G. 1973; Scrapie in mice: agent–strain differences in the distribution and intensity of grey matter vacuolation. Journal of Comparative Pathology 83:29–40
    [Google Scholar]
  30. Fraser H., Dickinson A. G. 1985; Targeting of scrapie lesions and spread of agent via the retino-tectal projection. Brain Research 346:32–41
    [Google Scholar]
  31. Goldgaber D., Goldfarb L. G., Brown P., Asher D. M., Brown W. T., Lin S., Teener J. W., Feinstone S. M., Rubenstein R., Kascsak R. J., Boellaard J. W., Gajdusek D. C. 1989; Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Straussler-Sheinker’s syndrome. Experimental Neurology 106:204–206
    [Google Scholar]
  32. Gregoire N., Nezri C., Gorde-Durand J. M., Bouras C., Bert J., Salamon G. 1984; Cerebral metabolic changes induced by an unconventional agent: experimental model for some human degenerative diseases of the central nervous system. Monographs in Neural Science 11:193–203
    [Google Scholar]
  33. 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. EMBO Journal 5:2591–2597
    [Google Scholar]
  34. Hsiao K., Baker H. F., Crow T. J., Poulter M., Owen F., Terwilliger J. D., Westaway D., Ott J., Prusiner S. B. 1989; Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome. Nature, London 338:342–345
    [Google Scholar]
  35. Hunter N., Hope J., McConnell I., Dickinson A. G. 1987; Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenic mice and restriction fragment length polymorphism analysis. Journal of General Virology 68:2711–2716
    [Google Scholar]
  36. Hunter N., Foster J. D., Dickinson A. G., Hope J. 1989; Linkage of the gene for the scrapie associated fibril protein (PrP) to the Sip gene in Cheviot sheep. Veterinary Record 124:364–366
    [Google Scholar]
  37. Kimberlin R. H., Walker C. A. 1978a; Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture. Journal of General Virology 39:487–496
    [Google Scholar]
  38. Kimberlin R. H., Walker C. A. 1978b; Pathogenesis of mouse scrapie: effect of route of inoculation on infectivity titres and dose-response curves. Journal of Comparative Pathology 88:39–47
    [Google Scholar]
  39. Kimberlin R. H., Walker C. A. 1979; Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. Journal of Comparative Pathology 89:551–562
    [Google Scholar]
  40. Kimberlin R. H., Walker C. A. 1986; Transport, targeting and replication of scrapie in the CNS. In Unconventional Virus Diseases of the Central Nervous System pp 547–562 Edited by Court L. A., Dormont D., Brown P., Kingsbury D. T. Fontenay-aux-Roses: Commissariat a l’Energie Atomique;
    [Google Scholar]
  41. Kimberlin R. H., Walker C. A. 1988; Pathogenesis of experimental scrapie. In Novel Infectious Agents and the Central Nervous System Ciba Foundation Symposium 135 pp 37–62 Edited by Bock G., Marsh J. Chichester: John Wiley;
    [Google Scholar]
  42. Kimberlin R. H., Walker C. A., Millson G. C., Taylor D. M., Robertson P. A., Tomlinson A. H., Dickinson A. G. 1983; Disinfection studies with two strains of mouse-passaged scrapie agent. Journal of Neurological Sciences 59:355–369
    [Google Scholar]
  43. Kimberlin R. H., Cole S., Walker C. A. 1987; Pathogenesis of scrapie is faster when infection is intraspinal instead of intracerebral. Microbial Pathogenesis 2:405–414
    [Google Scholar]
  44. Kimberlin R. H., Walker C. A., Fraser H. 1989; The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. Journal of General Virology 70:2017–2025
    [Google Scholar]
  45. Kingsbury D. T., Kasper K. C., Stites D. P., Watson J. D., Hogan R. N., Prusiner S. B. 1983; Genetic control of scrapie and Creutzfeldt-Jakob disease in mice. Journal of Immunology 131:491–496
    [Google Scholar]
  46. McBride P. A., Bruce M. E., Fraser H. 1988; Immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie-associated fibrils (SAF). Neuropatholology and Applied Neurobiology 14:325–336
    [Google Scholar]
  47. 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]
  48. Merz P. A., Somerville R. A., Wisniewski H. M., Iqbal K. 1981; Abnormal fibrils from scrapie-infected brain. Acta neuropathologica 54:63–74
    [Google Scholar]
  49. Oesch B., Groth D. F., Prusiner S. B., Weissmann C. 1988; Search for a scrapie-specific nucleic acid: a progress report. In Novel Infectious Agents and the Central Nervous System, Ciba Foundation Symposium 135 pp 209–223 Edited by Bock G., Marsh J. Chichester: John Wiley;
    [Google Scholar]
  50. Outram G. W. 1976; The pathogenesis of scrapie in mice. In Slow Virus Diseases of Animals and Man pp 325–357 Edited by Kimberlin R. H. Amsterdam: North-Holland;
    [Google Scholar]
  51. Owen F., Poulter M., Lofthouse R., Collinge J., Crow T. J., Risby D., Baker H. F., Ridley R. M., Hsiao K., Prusiner S. B. 1989; Insertion in prion protein gene in familial Creutzfeldt– Jakob disease. Lancet i:51–52
    [Google Scholar]
  52. Pattison I. H., Millson G. C. 1961; Scrapie produced experimentally in goats with special reference to the clinical syndrome. Journal of Comparative Pathology 71:101–108
    [Google Scholar]
  53. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    [Google Scholar]
  54. Race R. E., Graham K., Ernst D., Caughey B., Chesebro B. 1990; Analysis of linkage between scrapie incubation period and the prion protein gene in mice. Journal of General Virology 71:493–497
    [Google Scholar]
  55. Scott M., Foster D., Mirenda C., Serban D., Coufal F., Wälchli M., Torchia M., Groth D., Carlson G., DeArmond S. J., Westaway D., Prusiner S. B. 1989; Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59:847–857
    [Google Scholar]
  56. Somerville R. A., Merz P. A., Carp R. I. 1986; Partial copurification of scrapie-associated fibrils and scrapie infectivity. Intervirology 25:48–55
    [Google Scholar]
  57. Westaway D., Goodman P. A., Mirenda C. A., McKinley M. P., Carlson G. A., Prusiner S. B. 1987; Distinct prion proteins in short and long scrapie incubation period mice. Cell 51:651–662
    [Google Scholar]
  58. Wills P. R. 1989; Induced frameshifting mechanism of replication for an information-carrying scrapie prion. Microbial Pathogenesis 6:235–249
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-72-3-595
Loading
/content/journal/jgv/10.1099/0022-1317-72-3-595
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error