35 Classical Scrapie Resistance in Goats Based on S146

Abstract

Scrapie is the transmissible spongiform encephalopathy (TSE) of sheep and goats, and it can be transmitted in both directions between these species. Scrapie eradication programs worldwide have utilized strong genetic resistance to classical scrapie in sheep, but such resistance has not been available for goats until recently. Both S146 (serine at position 146) and K222 (lysine at position 222) amino acid substitutions in the prion protein have been dramatically underrepresented in natural scrapie cases, but exposure times are not known in most natural situations. Therefore, we used a goat classical scrapie homogenate to orally challenge: 1) 5 goat kids with control genotypes [two copies of the most common haplotype], 2) 8 kids with one copy of S146 and one copy of the control haplotype, and 3) 8 kids with one copy of S146 and one copy of the control haplotype. All control goats developed classical scrapie by an average age of 2 years, but there has been no confirmed scrapie in the S146 group by an average age of 7.8 years, or in the K222 group by an average age of 6.8 years (both P<0.001). Thus, goats with a single copy of either S146 or K222 have not developed classical scrapie for longer than the productive lifetimes of most commercial goats. Recently, the European Food Safety Authority convened a large panel to consider all the evidence from this experiment and many others. They concluded both S146 and K222 have more evidence for scrapie resistance today than sheep R171 did when it was first recommended as a source of resistance to classical scrapie in sheep. The panel recommended both S146 and K222 for use in scrapie programs. There are commercially available DNA testing services to identify S146 and K222, which occur naturally in many North American goats.