Scrapie-associated prion protein in the gastro-intestinal tract of sheep with natural scrapie.
In studies of ileal samples from 55 scrapie-positive and 12 scrapie-negative sheep the scrapie-associated form of the prion protein (PrPSc) accumulated in the enteric nervous system (ENS) of all scrapie-infected sheep but not in scrapie-negative sheep. The distribution of PrPSc within the ENS was then studied along the entire gastrointestinal tract in 7 scrapie-infected sheep carrying various PrP genotypes. In sheep with the highest genetically determined susceptibility to scrapie, PrPSc was detected in the ENS from the oesophagus to the rectum. In sheep with a lower genetic susceptibility to scrapie, PrPSc was present in the ENS of the forestomach, small intestine and large intestine but not in the oesophagus. In a scrapie-negative sheep with a PrP genotype associated with scrapie resistance, no PrPSc was seen in the ENS at any site along the gastrointestinal tract. It is concluded that the presence of PrPSc within the ENS of scrapie-infected sheep indicates a possible role of the ENS in the pathogenesis of natural scrapie as a portal of entry to the central nervous system.