NR AJIV
AU Peretz,D.; Williamson,R.A.; Legname,G.; Matsunaga,Y.; Vergara,J.; Burton,D.R.; DeArmond,S.J.; Prusiner,S.B.; Scott,M.R.D.
TI A change in the conformation of prions accompanies the emergence of a new prion strain
QU Neuron 2002 Jun 13; 34(6): 921-32
KI Neuron. 2002 Jun 13;34(6):854-6. PMID: 12086631
PT journal article
AB To investigate the role of the pathogenic prion protein (PrPsc) 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. PrPsc 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 PrPsc conformation, and the emergence of new prion strains.
MH Animal; Brain/pathology; *Crosses, Genetic; Goats; Hamsters; Human; Mesocricetus; Mice; Mice, Transgenic; Phenotype; PrPsc Proteins/*chemistry/genetics; Prion Diseases/etiology/genetics/*metabolism/*transmission; Protein Conformation; Rats; Species Specificity; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, CA 94143, USA
SP englisch
PO USA