Distinct Proteinase K-Resistant Prion Protein Fragment in Goats with No Signs of Disease in a Classical Scrapie Outbreak†

Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrPres) in a highly scrapie-affected goat flock in Greece. The PrPres profile by Western immunoblotting in most animals was that of classical scrapie in sheep. However, in a series of clinically healthy goats we identified a unique C- and N-terminally truncated PrPres fragment, which is akin but not identical to that observed for atypical scrapie. These findings reveal novel aspects of the nature and diversity of the molecular PrPres phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder. Classical scrapie is a fatal contagious disease that naturally affects sheep and goats. Together with Creutzfeldt-Jakob dis-ease (CJD) and bovine spongiform encephalopathy (BSE) in cattle, it figures among the transmissible spongiform enceph-alopathies (TSE) or prion diseases (25). These are lethal neu-rodegenerative disorders that show neuropil spongiosis as well as intraneuronal vacuolation, astrocytic gliosis, and the depo