title: A change in the conformation of prions accompanies the emergence of a new prion strain.
abstract: To investigate the role of the pathogenic prion protein (PrP(Sc)) in controlling susceptibility to foreign prions, two Syrian hamster (SHa) prion strains, Sc237 and DY, were transmitted to transgenic mice expressing chimeric SHa/mouse PrP genes, Tg(MH2M). First passage of SHa(Sc237) prions exhibited prolonged incubation times, diagnostic of a species barrier. PrP(Sc) of the new MH2M(Sc237) strain possessed different structural properties from those of SHa(Sc237), as demonstrated by relative conformational stability measurements. This change was accompanied by a disease phenotype different from the SHa(Sc237) strain. Conversely, transmission of SHa(DY) prions to Tg(MH2M) mice showed no species barrier, and the MH2M(DY) strain retained the conformational and disease-specific properties of SHa(DY). These results suggest a causal relationship between species barriers, changes in PrP(Sc) conformation, and the emergence of new prion strains.
authors.affiliation: Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: David
authors.initials: D
authors.lastname: Peretz
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Williamson
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Julie
authors.initials: J
authors.lastname: Vergara
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Scott
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D006224:Cricetinae; D003433:Crosses, Genetic; D006041:Goats; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018620:PrPSc Proteins / Q000737:chemistry* / Q000235:genetics; D017096:Prion Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000635:transmission*; D011487:Protein Conformation; D051381:Rats; D013045:Species Specificity
chemical_list: D018620:PrPSc Proteins