Bovine spongiform encephalopathy agent in a prion protein (PrP)ARR/ARR genotype sheep after peripheral challenge: complete immunohistochemical analysis of disease-associated PrP and transmission studies to ovine-transgenic mice.

Possible transmission of the bovine spongiform encephalopathy (BSE) agent to ovine species has been considered for several years. It has been recently demonstrated that the BSE agent, after intracerebral challenge, can infect sheep believed to be the most resistant genetically to prion diseases (prion protein [PrP](ARR/ARR) genotype). We report here the results of a detailed immunohistochemical analysis of the disease-associated PrP (PrP(d)) in all organs from a PrP(ARR/ARR) sheep infected with the BSE agent by a peripheral route. Because PrP(d) was detected in the brain in the absence of any clinical symptoms, transmission studies were also performed using a sensitive ovine-transgenic mouse model--Tg(OvPrP4)--that can identify the BSE agent on the basis of the occurrence of florid plaques in the mouse brain. The data indicated that these PrP(d) deposits were linked to the BSE agent and were associated with infectivity. This suggests that PrP(ARR/ARR) sheep may be silent carriers of the BSE agent.