Popis: |
Scrapie is the transmissible spongiform encephalopathy of sheep and goats, and scrapie eradication efforts are underway in many countries. Goats may serve as a scrapie reservoir and to date there has been no experimental inoculation confirming strong, lifelong genetic resistance in goats. Goats bearing S146 or K222 amino acid substitutions in the prion protein have been present in scrapie-exposed herds but significantly underrepresented in disease cases. Furthermore, both variant proteins give low cell-free protein conversion efficiency to the disease form, PrPSc. To ensure consistent exposure, we performed oral scrapie challenge of goats singly heterozygous for either S146 or K222. All controls homozygous for the most common haplotype showed clinical scrapie by an average of 24 months post-inoculation; in contrast, none of the S146 and K222 heterozygotes have scrapie-positive lymphoid biopsy tests or confirmed scrapie at incubation times now approaching 7 years or longer (P |