Use of Murine Bioassay to Resolve Ovine Transmissible Spongiform Enchephalopathy Cases showing a Bovine Spongiform Encephalopathy Molecular Profile

Two cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and sub-passage, incubation period (IP) of disease, PrP(Sc) immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterise the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild type mice; PrP(Sc) deposition pattern in wild type mice; IP and Western blot data in transgenic mice. Furthermore, IHC revealed that each case generated two distinct PrP(Sc) deposition patterns in both wild type and transgenic mice suggesting that two scrapie strains co-existed in the ovine hosts. Critically, these data confirmed the original differential IHC categorisation that these UK-1 and UK-2 cases were not compatible with BSE