Resistance to classical scrapie in experimentally challenged goats carrying mutation K222 of the prion protein gene

Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) of sheep and goats, characterized by the accumulation in the central nervous system (CNS) of an abnormal isoform (PrPSc) of a host-encoded cellular prion protein (PrPC) [1]. Natural scrapie in goats was first reported in France [2], followed by other cases worldwide: a state of the art review on goat scrapie in the European Union, including its epidemiology, was published by Vaccari et al. [3]. Goats are susceptible not only to classical scrapie, but also atypical/Nor98 scrapie cases have been detected. As in sheep, it is characterized by distinctive features in epidemiology (i.e., occurrence as single cases in the affected herds), molecular pattern, and distribution of histopathological changes [3]. Moreover, the only two confirmed cases of natural bovine spongiform encephalopathy (BSE) in small ruminants were reported in goats in France [4] and in a retrospective study in the UK [5].The first Italian case of scrapie in the goat was diagnosed in 1997 [6]; since then, 65 outbreaks have occurred (51 of classical scrapie and 14 of Nor98 scrapie), in which 13 000 goats were culled in accordance with the foreseen measures for eradication of the disease.Although an infectious disease, the susceptibility of sheep to scrapie is strongly influenced by polymorphisms of the prion protein gene (PRNP). PRNP haplotypes valine/arginine/glutamine (VRQ) and alanine/arginine/glutamine (ARQ) at codons 136, 154, 171, respectively, are associated with high susceptibility to classical scrapie, whereas the ARR haplotype has been linked to resistance [7-10]. Accordingly, the EU has implemented breeding programs to increase scrapie resistance in sheep populations. In compliance with regulation (EC) 999/2001, as amended, several Member States are now increasing the frequency of the ARR haplotype. A similar approach has not yet been applied in goats, but it would be desirable in this species too, given that scrapi