Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie

The scrapie-associated prion protein (PrPSc), which is closely associated w ith scrapie infectivity, accumulates in the brain and lymphoid tissues of s heep with natural scrapie. The most probable portal of entry of the scrapie agent in sheep is the alimentary tract; little attention, however, has bee n paid to the gastro-intestinal tract in scrapie research. In this study, w e examined the presence and distribution of PrPSc within the gastro-intesti nal tract of sheep with natural scrapie and scrapie-negative sheep. It was found that PrPSc accumulated in the enteric nervous system (ENS) of all scr apie-infected sheep but not in scrapie-negative sheep. The distribution of PrPSc within the ENS was then studied along the entire gastro-intestinal tr act in seven scrapie-infected sheep carrying various PrP genotypes. In shee p 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 th e forestomachs, small intestine and large intestine but not in the oesophag us. 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 gastro-inte stinal tract. The presence of PrPSc within the ENS of scrapie-infected shee p indicates a possible role of the ENS in the pathogenesis of natural scrap ie as a portal of entry to the central nervous system (C) 1999 W.B. Saunder s Company Limited.