1887

Abstract

The prion protein (PrP) gene modulates the incidence and incubation periods of transmissible spongiform encephalopathies of sheep, goats, mice and man. Here, a new caprine PrP allele encoding the shortest naturally occurring PrP protein so far described is reported. This variant contains only three instead of the usual five copies of a short peptide repeat [Pro-Gln/His-Gly-Gly-Gly-(Gly)-Trp- Gly-Gln] characteristic of PrP, with an additional Trp to Gly substitution in codon 102. Fifteen out of 111 genotyped goats carried the novel PrP allele and 14 survived without signs of disease for at least 4 years. One goat heterozygous for the polymorphism was challenged experimentally with SSBP/1-scrapie and succumbed after an unusually long incubation period.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-12-3173
1998-12-01
2022-05-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/12/9880037.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-12-3173&mimeType=html&fmt=ahah

References

  1. Brown P. 1994; Transmissible human spongiform encephalopathy (infectious cerebral amyloidosis): Creutzfeldt-lakob disease, Gerstmann- Straussler-Scheinker syndrome, and Kuru. In Neurodegenerative Diseases pp 839–876 Calne D. B. Edited by Philadelphia: W. B. Saunders;
    [Google Scholar]
  2. Brown D. R., Qin K., Herms J. W., Madlung A., Manson J., Strome R., Fraser P. E., Kruck T., von Bohlens A., Schulz-Schaeffer W., Giese A., Westaway D., Kretzschmar H. 1997; The cellular prion protein binds copper in vivo . Nature 390:684–687
    [Google Scholar]
  3. Cervenakova L., Brown P., Nagle J., Goldfarb L. G., Gajdusek D. C. 1994; R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD). American Journal of Human Genetics 55:3
    [Google Scholar]
  4. Chen S. G., Teplow D. B., Parchi P., Teller J. K., Gambetti P., Autiliogambetti L. 1995; Truncated forms of the human prion protein in normal brain and in prion diseases. Journal of Biological Chemistry 270:19173–19180
    [Google Scholar]
  5. Diedrich J. F., Knopman D. S., List J. F., Olson K., Frey W. H. II Emory C. R., Sung J. H., Haase A. T. 1992; Deletion in the prion protein gene in a demented patient. Human Molecular Genetics 1:443–444
    [Google Scholar]
  6. Farquhar C. F., Somerville R. A., Ritchie L. A. 1989; Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy. Journal of Virological Methods 24:215–221
    [Google Scholar]
  7. Fischer M., Rlicke T., Raeber A., Sailer A., Moser M., Oesch B., Brandner S., Aguzzi A., Weissmann C. 1996; Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO Journal 15:1255–1264
    [Google Scholar]
  8. Goldfarb L. G., Brown P., McCombie W. R., Goldgaber D., Swergold G. D., Wills P. R., Cervenakova L., Baron H., Gibbs C. J. Jr 1991; Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. roceedings of the National Academy of Sciences, USA 88:10926–10930
    [Google Scholar]
  9. Goldmann W., Hunter N., Foster J. D., Salbaum J. M., Beyreuther K., Hope J. 1990; Two alleles of a neural protein gene linked to scrapie in sheep. Proceedings of the National Academy of Sciences, USA 87:2476–2480
    [Google Scholar]
  10. Goldmann W., Hunter N., Martin T., Dawson M., Hope J. 1991; Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. Journal of General Virology 72:201–204
    [Google Scholar]
  11. Goldmann W., Martin T., Foster J., Hughes S., Smith G., Hughes K., Dawson M., Hunter N. 1996; Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period. Journal of General Virology 77:2885–2891
    [Google Scholar]
  12. 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]
  13. Hornshaw M. P., McDermott J. R., Candy J. M. 1995; Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochemical and Biophysical Research Communications 207:621–629
    [Google Scholar]
  14. Hunter N. 1997; Molecular biology and genetics of scrapie in sheep. In The Genetics of Sheep pp 225–240 Piper L., Ruvinsky A. Edited by Wallingford, UK: CAB International;
    [Google Scholar]
  15. Hunter N., Goldmann W., Smith G., Hope J. 1994; Frequencies of PrP gene variants in healthy cattle and cattle with BSE in Scotland. Veterinary Record 135:400–403
    [Google Scholar]
  16. Hunter N., Foster J. D., Goldmann W., Stear M., Hope J., Bostock C. 1996; Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology 141:809–824
    [Google Scholar]
  17. Kenney K., Brown P., Little B. 1995; Insert mutation in Creutzfeldt-Jakob disease. Neurology 45:1428
    [Google Scholar]
  18. Kretzschmar H., Stowring L. E., Westaway D., Stubblebine W. H., Prusiner S. B., DeArmond S. B. 1986; Molecular cloning of a human prion protein cDNA. DNA 5:315–324
    [Google Scholar]
  19. Laplanche J. L., Delasnerie-Laupretre N., Brandel J. P., Dussaucy M., Chatelain J., Launay J. M. 1995; Two novel insertions in the prion protein gene in patients with late-onset dementia. Human Molecular Genetics 4:1109–1111
    [Google Scholar]
  20. Manson J. C., Clarke A. R., McBride P. A., McConnell I., Hope J. 1994; PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegeneration 3:331–340
    [Google Scholar]
  21. Palmer M. S., Mahal S. P., Campbell T. A., Hill A. F., Sidle K. C., Laplanche J.-L., Collinge J. 1993; Deletions in the prion protein gene are not associated with CJD. Human Molecular Genetics 2:541–544
    [Google Scholar]
  22. Sambrook J., Fritsch F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  23. Schätzl H. M., DaCosta M., Taylor L., Cohen F. E., Prusiner S. B. 1995; Prion protein gene variation among primates. Journal of Molecular Biology 245:362–374
    [Google Scholar]
  24. Stöckel J., Safar J., Wallace A. C., Cohen F. E., Prusiner S. B. 1998; Prion protein selectively binds copper(II) ions. Biochemistry 37:7185–7193
    [Google Scholar]
  25. Vital C., Gray F., Vital A., Parchi P., Capellari S., Petersen R. B., Ferrer X., Jarnier D., Julien J., Gambetti P. 1998; Prion encephalopathy with insertion of octapeptide repeats : the number of repeats determines the type of cerebellar deposits. Neuropathology and Applied Neurobiology 24:125–130
    [Google Scholar]
  26. Wood J. N. L., Done S. H., Pritchard G. C., Wooldridge M. J. A. 1992; Natural scrapie in goats : case histories and clinical signs. Veterinary Record 131:66–68
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-12-3173
Loading
/content/journal/jgv/10.1099/0022-1317-79-12-3173
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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