The pathobiology of atypical
scrapie, a
prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical
scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological
prion protein (
PrP(d)). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical
scrapie to transgenic mice over-expressing the ovine
prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical
scrapie isolates and the Nor98, an atypical
scrapie isolate from Norway. Together with published data, our results suggest that atypical
scrapie is caused by a uniform type of
prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent
proteinase K-resistant
prion protein fragment in atypical
scrapie consists of two separate, unglycosylated
peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other
prion diseases in animals and humans, and lay the groundwork for future comparative research.