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Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene ( PRNP ) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrP Sc  in affected sheep. The purpose of this study was to compare the survival time and PrP Sc  tissue distribution in sheep with highly resistant and highly susceptible  PRNP  genotypes after intracranial inoculation of the agent of scrapie. Five sheep each of genotype VRQ/VRQ, VRQ/ARR or ARQ/ARR were inoculated. Sheep were euthanized when clinical signs of scrapie became severe. Clinical signs, microscopic lesions, and western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ sheep surviving 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Labeling of PrP Sc  by immunohistochemistry revealed similar accumulations in central nervous system tissues regardless of host genotype. Immunoreactivity for PrP Sc  in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrP Sc  accumulation in CNS tissues, but prolonged incubation times and lack of PrP Sc  in lymphoid tissue.

Lack of Prion Accumulation in Lymphoid Tissues of PRNP ARQ/ARR Sheep Intracranially Inoculated with the Agent of Scrapie