Goats Singly Heterozygous for PRNP S146 or K222 Substitutions Each Show Extended Scrapie Incubation Time Beyond Common Commercial Productive Lifetime
International Plant & Animal Genome XXV, San Diego, United States Of America, 14 - 18 January 2017, pp.117-118, (Summary Text)
- Publication Type: Conference Paper / Summary Text
- City: San Diego
- Country: United States Of America
- Page Numbers: pp.117-118
- Erciyes University Affiliated: Yes
Abstract
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<0.0001). Recent reports identified natural scrapie in less than five S146 and K222 heterozygotes, suggesting heterozygotes will not have truly complete resistance. However, scrapie incubation times are now as long as or longer than many commercial operations keep goats for production purposes, so S146 or K222 may reduce the probability of clinical scrapie during commercial goat productive life spans. These results also suggest much longer relevant trace-back histories for goats of these genotypes in scrapie-eradication programs. Finally, these data support additional consideration of potential scrapie resistance in homozygotes for these alleles, since to our knowledge there have never been natural scrapie positives in homozygotes for either allele.