Location: Animal Disease ResearchTitle: Role of PRNP S127 allele in experimental goat infection with classical caprine scrapie Author
|Dassanayake, Rohana - Washington State University|
|Madsen-bouterse, Sally - Washington State University|
|O'rourke, Katherine - Washington State University|
Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/7/2015
Publication Date: 6/1/2015
Citation: Dassanayake, R.P., White, S.N., Madsen-Bouterse, S.A., Schneider, D.A., O'Rourke, K.I. 2015. Role of PRNP S127 allele in experimental goat infection with classical caprine scrapie. Animal Genetics. doi: 10.1111/age.12291.
Interpretive Summary: Classical scrapie is a transmissible spongiform encephalopathy that affects domestic goats and sheep. Even if current scrapie eradication measures are successful in sheep, goats can act as a scrapie reservoir and transmit scrapie to sheep. Scrapie eradication in sheep is based in part on strong genetic resistance to the classical scrapie. However, implications of differing genotypes have been less well explored in goats. In particular, one prion gene polymorphism at codon 127 (G/S127; G=glycine, S=serine) is significantly underrepresented in scrapie infected goats but the specific scrapie incubation period has not been defined for the G/S127 genotype goats. Therefore, the aim of this study was to identify whether goats with the G/S127 genotype have extended incubation periods with classical caprine scrapie. Challenge experiments demonstrated control goats of the G/G127 genotype had scrapie incubation periods of 261-332 days while G/S127 genotype goats had incubation periods of 647-1333 days. These results suggest that scrapie eradication programs should include longer traceback history for G/S127 genotype goats compared to G/G127 genotype goats.
Technical Abstract: Classical scrapie is a transmissible spongiform encephalopathy that affects domestic goats and sheep. Experimental inoculation studies in sheep confirmed that classical caprine scrapie can readily transmit to sheep. Therefore, even if current scrapie eradication measures are successful in sheep, goats can act as a scrapie reservoir for sheep. Scrapie eradication in sheep is based in part on strong genetic resistance to the classical scrapie. Like the prion gene (PRNP) of sheep, PRNP of goats is highly polymorphic. Experimental classical caprine scrapie inoculation studies using goats revealed that PRNP polymorphisms at codons 146, 154, 211 and 222 can provide resistance to scrapie following oral inoculation but were unable protect upon intracerebral inoculation. Polymorphism at codon 142 was not protective and provided only a moderate increase of incubation period. A recent study has identified an association between a polymorphism at codon 127 (G/S127) and reduced probability to develop clinical scrapie, but the length of incubation period was not defined. Therefore, the aim of this study was to identify whether goats with heterozygous G/S127 genotype have extended incubation period following caprine scrapie inoculation. No significant difference in incubation time was observed for homozygous G/G127 versus heterozygous G/S127 inoculum in recipient homozygous G/G127 goats (P=0.30). In contrast, a significant (P=0.019) increase in the incubation period was observed in heterozygous G/S127 goats following an intracerebral inoculation with a homozygous G/G127 caprine scrapie inoculum. All the scrapie inoculated recipient goats developed clinical scrapie and scrapie prion accumulation was detected in all the brains and most of the lymphoid tissues. These findings suggest the need of a longer relevant traceback history in scrapie eradication programs for goats with the heterozygous G/S127 PRNP polymorphism compared to the homozygous G/G127 goats.