Isolates or """"""""strains"""""""" of scrapie prions possess and retain distinct phenotypes when serially passaged in a given species. The information for their distinct, inherited traits must be contained within the infectious prion particle yet there is no evidence, to date, for a scrapie specific nucleic acid. The existence of these isolates constitutes a touchstone for any model of prion replication and structure. The goal of this proposal is to compare two distinct isolates of hamster scrapie prions in cultured cells. These isolates, designated Sc237 and 139H, differ dramatically in their incubation times in Syrian hamsters. The Sc237 isolate causes in about 70 days while the 139H isolate cause disease in about 150 days. Using SH cells, a novel prion-infectible hamster cell line, the """"""""genetics"""""""" of these two isolates will be studied by experiments designed to assess their stability in tissue culture, the appearance of mutations, and phenotypical mixing. The biochemical characteristics of the PrPSc synthesized in SH cells infected with each isolate will be compared. The proposed study may begin to unravel biological and molecular differences between these isolates and thus begin to clarify the concept of scrapie prion """"""""strains"""""""".
| Supattapone, S; Muramoto, T; Legname, G et al. (2001) Identification of two prion protein regions that modify scrapie incubation time. J Virol 75:1408-13 |
| Zulianello, L; Kaneko, K; Scott, M et al. (2000) Dominant-negative inhibition of prion formation diminished by deletion mutagenesis of the prion protein. J Virol 74:4351-60 |
| Baskakov, I V; Aagaard, C; Mehlhorn, I et al. (2000) Self-assembly of recombinant prion protein of 106 residues. Biochemistry 39:2792-804 |
| Scott, M R; Supattapone, S; Nguyen, H O et al. (2000) Transgenic models of prion disease. Arch Virol Suppl :113-24 |
| Kaneko, K; Ball, H L; Wille, H et al. (2000) A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice. J Mol Biol 295:997-1007 |
| Mastrianni, J A; Nixon, R; Layzer, R et al. (1999) Prion protein conformation in a patient with sporadic fatal insomnia. N Engl J Med 340:1630-8 |
| Supattapone, S; Nguyen, H O; Cohen, F E et al. (1999) Elimination of prions by branched polyamines and implications for therapeutics. Proc Natl Acad Sci U S A 96:14529-34 |
| Scott, M R; Will, R; Ironside, J et al. (1999) Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci U S A 96:15137-42 |
| Safar, J; Prusiner, S B (1998) Molecular studies of prion diseases. Prog Brain Res 117:421-34 |
| Prusiner, S B (1998) The prion diseases. Brain Pathol 8:499-513 |
Showing the most recent 10 out of 85 publications
