Location: Animal Disease ResearchTitle: Goats singly heterozygous for PRNP S146 or K222 orally inoculated with classical scrapie at birth show no disease at ages well beyond six years
|CINAR ULAS, MEHMET - Erciyes University|
|WALDRON, DANIEL - Texas A&M Agrilife|
Submitted to: Journal of Animal Breeding and Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/23/2017
Publication Date: 2/24/2018
Citation: Cinar Ulas, M., Schneider, D.A., Waldron, D.F., O'Rourke, K., White, S.N. 2018. Goats singly heterozygous for PRNP S146 or K222 orally inoculated with classical scrapie at birth show no disease at ages well beyond six years. Journal of Animal Breeding and Genetics. 233:19-24.
Interpretive Summary: Scrapie is the transmissible spongiform encephalopathy of sheep and goats. In previous work, we used oral scrapie challenge to show significantly extended incubation in goats singly heterozygous for prion amino acid substitutions S146 or K222, but average disease-free periods were only around 3 years. The aim of the present work was to investigate whether the disease-free period would exceed 6 years as representative of productive lifetimes for most commercial goats. While all control homozygotes became clinically scrapie positive by an average of less than 2 years, no goats with one copy of either S146 or K222 have developed scrapie. The goats with one copy of S146 have remained disease-free for an average of 7.5 years, and this is the longest disease-free incubation period for any classical scrapie challenge experiment with any genotype to date. The goats with one copy of K222 have remained disease-free for an average of 6.7 years, and this is the longest reported average disease-free incubation time for K222 single copy goats challenged with classical scrapie to date. Our results confirm the strong resistance to classical scrapie conferred by S146 and K222, and our experiment is ongoing to assess the full extent of incubation times for S146 and K222 goats. These data add to growing evidence that selectively breeding goats to avoid scrapie may be possible using the S146 and K222 alleles.
Technical Abstract: Scrapie is a transmissible spongiform encephalopathy of sheep and goats, and scrapie eradication programs in many parts of the world rely on strong genetic resistance to classical scrapie in sheep. However, the utility of putative resistance alleles in goats has been a focus of research because goats can transmit scrapie to sheep and may serve as a scrapie reservoir. Prior work showed that disease-free survival time was significantly extended in orally inoculated goats singly heterozygous for prion amino acid substitutions S146 or K222, but average durations were only around 3 years post-inoculation. The aim of this study was to investigate whether extended survival would exceed 6 years, which represents the productive lifetimes of most commercial goats. While all control homozygotes were clinically affected by an average of <2 years, none of the NS146 or QK222 goats developed clinical scrapie or had PrPSc-positive rectal biopsies. Several NS146 and QK222 goats developed other conditions unrelated to scrapie, but tissue accumulation of PrPSc was not detected in any of these animals. The NS146 heterozygotes have remained disease-free for an average of 2734 days (approximately 7.5 years), the longest duration of any classical scrapie challenge experiment with any genotype to date. The QK222 heterozygotes have remained disease-free for an average of 2450 days (approximately 6.7 years), the longest reported average duration for QK222 goats challenged with classical scrapie. This research is ongoing, but the current results demonstrate S146 and K222 confer strong resistance to classical scrapie in goats.