5 years ago

The effect of polymorphisms at codon 146 of the goat PRNP gene on susceptibility to challenge with classical scrapie by different routes.

Simmons MM, Ortiz-Pelaez A, Spiropoulos J, Papasavva-Stylianou P, Georgiadou S, Windl O
This report presents the results of experimental challenges of goats with scrapie by both the intracerebral and oral routes, exploring the effects of polymorphisms at codon 146 of the goat PRNP gene on resistance to disease. The results of these studies illustrate that while goats of all genotypes can be infected by intracerebral (ic) challenge, the survival distribution of the animals homozygous for asparagine at codon 146 was significantly shorter than for all other genotypes (chi2 =10.8. P=0.001). In contrast, only those animals homozygous for asparagine at codon 146 (NN) succumb to oral challenge. The results also indicate that any cases in non-NN animals can be detected by the current confirmatory test (immunohistochemistry), although successful detection with the ELISA rapid test was more variable, and dependent on the polymorphism. Together with previous studies of goats exposed to infection in the field, these data support the previously published observations that polymorphism at this codon has a profound effect on susceptibility to disease. It is concluded that only animals homozygous for asparagine at codon 146 succumb to scrapie under natural conditions.IMPORTANCE In goats, like in sheep, there are PRNP polymorphisms which are associated with susceptibility/resistance to scrapie. However, in contrast to sheep, they are more numerous and may be restricted to certain breeds or geographical regions. Therefore, eradication programs must be specifically designed depending on the identification of suitable polymorphisms. Initial analysis of surveillance data suggested that such a polymorphism in Cypriot goats may lie in codon 146. In this study, we demonstrate experimentally that NN animals are highly susceptible after ic inoculation. Presence of D or S prolonged incubation periods significantly and only in NN animals prions were detected in peripheral tissues. In oral challenges, prions were detected only in NN animals and presence of D or S at this position conferred resistance to the disease. This study provides an experimental transmission model for assessing genetic susceptibility of goats to scrapie.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28878088

DOI: PubMed:28878088

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