1887

Abstract

Prion diseases in ruminants, especially sheep scrapie, cannot be fully explained by genetics, suggesting the influence of a second modulator gene. The gene is a good candidate for this role. The gene encodes the shadoo protein (Sho) which has homology to the gene encoding prion protein (PrP). Murine Sho has a similar neuroprotective activity to PrP and gene variants are associated with human prion disease susceptibility. gene sequences were obtained from 14 species in the orders Artiodactyla and Rodentia. We report here the sequences of more than 20 different Sho proteins that have arisen due to single amino acid substitutions and amino acid deletions or insertions. All Sho sequences contained an alanine-rich sequence homologous to a hydrophobic region with amyloidogenic characteristics in PrP. In contrast with PrP, the Sho sequence showed variability in the number of alanine residues.

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2009-10-01
2024-05-06
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References

  1. Beck J. A., Campbell T. A., Adamson G., Poulter M., Uphill J. B., Molou E., Collinge J., Mead S. 2008; Association of a null allele of SPRN with variant Creutzfeldt–Jakob Disease. J Med Genet 45:813–817 [CrossRef]
    [Google Scholar]
  2. Chesebro B. 1999; Prion protein and the transmissible spongiform encephalopathy diseases. Neuron 24:503–506 [CrossRef]
    [Google Scholar]
  3. Chiarini L. B., Freitas A. R., Zanata S. M., Brentani R. R., Martins V. R., Linden R. 2002; Cellular prion protein transduces neuroprotective signals. EMBO J 21:3317–3326 [CrossRef]
    [Google Scholar]
  4. Forloni G., Angeretti N., Chiesa R., Monzani E., Salmona M., Bugiani O., Tagliavini F. 1993; Neurotoxicity of a prion protein fragment. Nature 362:543–546 [CrossRef]
    [Google Scholar]
  5. Gasset M., Baldwin M. A., Lloyd D. H., Gabriel J. M., Holtzman D. M., Cohen F., Fletterick R., Prusiner S. B. 1992; Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. Proc Natl Acad Sci U S A 89:10940–10944 [CrossRef]
    [Google Scholar]
  6. Genoud N., Behrens A., Arrighi I., Aguzzi A. 2003; Prion proteins and infertility: insight from mouse models. Cytogenet Genome Res 103:285–289 [CrossRef]
    [Google Scholar]
  7. Goldmann W. 2008; PrP genetics in ruminant transmissible spongiform encephalopathies. Vet Res 39:30 [CrossRef]
    [Google Scholar]
  8. Gossner A. G., Bennet N., Hunter N., Hopkins J. 2009; Differential expression of Prnp and Sprn in scrapie infected sheep also reveals Prnp genotype specific differences. Biochem Biophys Res Commun 378:862–866 [CrossRef]
    [Google Scholar]
  9. Hegde R. S., Mastrianni J. A., Scott M. R., DeFea K. A., Tremblay P., Torchia M., DeArmond S. J., Prusiner S. B., Lingappa V. R. 1998; A transmembrane form of the prion protein in neurodegenerative disease. Science 279:827–834 [CrossRef]
    [Google Scholar]
  10. Hu W., Rosenberg R. N., Stüve O. 2007; Prion proteins: a biological role beyond prion diseases. Acta Neurol Scand 116:75–82 [CrossRef]
    [Google Scholar]
  11. Lampo E., Van Poucke M., Hugot K., Hayes H., Van Zeveren A., Peelman L. J. 2007; Characterization of the genomic region containing the Shadow of Prion Protein ( SPRN ) gene in sheep. BMC Genomics 8:138 [CrossRef]
    [Google Scholar]
  12. Lampo E., Van Poucke M., Vandesompele J., Erkens T., Van Zeveren A., Peelman L. J. 2009; Positive correlation between relative mRNA expression of PRNP and SPRN in cerebral and cerebellar cortex of sheep. Mol Cell Probes 23:60–64 [CrossRef]
    [Google Scholar]
  13. Mallucci G. R., Campbell T. A., Dickinson A., Beck J., Holt M., Plant G., de Pauw K. W., Hakin R. N., Clarke C. E. other authors 1999; Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene. Brain 122:1823–1837 [CrossRef]
    [Google Scholar]
  14. Manson J. C., Tuzi N. L. 2001; Transgenic models of the transmissible spongiform encephalopathies. Expert Rev Mol Med 3:1–15 [CrossRef]
    [Google Scholar]
  15. McIntyre K. M., Gubbins S., Goldmann W., Hunter N., Baylis M. 2008; Epidemiological characteristics of classical scrapie outbreaks in 30 sheep flocks in the United Kingdom. PLoS One 3:e3994 [CrossRef]
    [Google Scholar]
  16. Norstrom E. M., Mastrianni J. A. 2005; The AGAAAAGA palindrome in PrP is required to generate a productive PrPSc–PrPC complex that leads to prion propagation. J Biol Chem 280:27236–27243 [CrossRef]
    [Google Scholar]
  17. Peletto S., Perucchini M., Acín C., Dalgleish M., Reid H. W., Rasero R., Sacchi P., Stewart P., Caramelli M. other authors 2009; Genetic variability of the PRNP gene in wild ruminants from Italy and Scotland. J Vet Sci 10:115–120 [CrossRef]
    [Google Scholar]
  18. Perucchini M., Griffin K., Miller M. W., Goldmann W. 2008; PrP genotypes of free-ranging wapiti ( Cervus elaphus nelsoni ) with chronic wasting disease. J Gen Virol 89:1324–1328 [CrossRef]
    [Google Scholar]
  19. Premzl M., Gamulin V. 2007; Comparative genomic analysis of prion genes. BMC Genomics 8: 1 [CrossRef]
    [Google Scholar]
  20. Premzl M., Sangiorgio L., Strumbo B., Marshall Graves J. A., Simonic T., Gready J. E. 2003; Shadoo, a new protein highly conserved from fish to mammals and with similarity to prion protein. Gene 314:89–102 [CrossRef]
    [Google Scholar]
  21. Premzl M., Gready J. E., Jermiin L. S., Simonic T., Marshall Graves J. A. 2004; Evolution of vertebrate genes related to prion and Shadoo proteins – clues from comparative genomic analysis. Mol Biol Evol 21:2210–2231 [CrossRef]
    [Google Scholar]
  22. Uboldi C., Paulis M., Guidi E., Bertoni A., Meo G. P., Perucatti A., Iannuzzi L., Raimondi E., Brunner R. M. other authors 2006; Cloning of the bovine prion-like Shadoo (SPRN) gene by comparative analysis of the predicted genomic locus. Mamm Genome 17:1130–1139 [CrossRef]
    [Google Scholar]
  23. Uelhoff A., Tatzelt J., Aguzzi A., Winklhofer K. F., Haass C. 2005; A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein. J Biol Chem 280:5137–5140 [CrossRef]
    [Google Scholar]
  24. Watts J. C., Westaway D. 2007; The prion protein family: diversity, rivalry, and dysfunction. Biochim Biophys Acta 1772:654–672 [CrossRef]
    [Google Scholar]
  25. Watts J. C., Drisaldi B., Ng V., Yang J., Strome B., Horne P., Sy M. S., Yoong L., Young R. other authors 2007; The CNS glycoprotein Shadoo has PrP(C)-like protective properties and displays reduced levels in prion infections. EMBO J 26:4038–4050 [CrossRef]
    [Google Scholar]
  26. Zanata S. M., Lopes M. H., Mercadante A. F., Hajj G. N., Chiarini L. B., Nomizo R., Freitas A. R., Cabral A. L., Lee K. S. other authors 2002; Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J 21:3307–3316 [CrossRef]
    [Google Scholar]
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