3 SCRAPIE PRION ISOLATES EXHIBIT DIFFERENT ACCUMULATION PATTERNS OF THE PRION PROTEIN SCRAPIE ISOFORM

To investigate the molecular basis of prion diversity, we inoculated t ransgenic mice expressing the Syrian hamster prion protein (PrP) with three distinct prion isolates. We compared the three isolates designat ed Sc237, 139H, and Me7H in Tg(SHaPrP)7 mice with clinical signs of sc rapie because the incubation times with these mice are considerably sh orter than the times found with hamsters. Each prion isolate produced a distinctive pattern of the scrapie isoform of PrP (PrP(Sc)) accumula tion, as determined by histoblotting, a technique developed for the re gional mapping of PrP(Sc) deposition. The PrP(Sc) pattern with the Me7 H isolate was particularly interesting because it appeared to be confi ned to the hypothalamus and related structures-including the interstit ial nucleus of the stria terminalis, the paraventricular nucleus of th e thalamus, and periaqueductal grey. Additionally, the regions of PrP( Sc) accumulation remained highly restricted, even though the incubatio n time for Me7H scrapie was significantly longer than with Sc237 and 1 39H isolates. Neuropathological changes characterized by neuronal vacu olation and astrocytic gliosis were confined to those regions where Pr P(Sc) accumulated. These findings argue that the cell-specific propaga tion of prion isolates may be responsible for different properties exh ibited by each of the isolates.