The Roslin Institute
Sheep are the natural hosts of scrapie, a transmissible spongiform encephalopathy (TSE) infection controlled by PrP genotype. Animals of some genotypes, for example VRQ/VRQ, are at very high risk of disease, whereas other genotypes, such as ARR/ARR, are resistant. The use of experimental infections with different scrapie strains and with BSE has allowed us to observe that pathogenesis in different susceptible genotypes varies. VRQ/VRQ scrapie infected sheep have PrPSC deposits in lymphoid tissues prior to involvement of the central nervous system and, as clinical neurodegenerative signs start to occur, PrPSC is detected in the brain. Sheep of VRQ/ARQ and VRQ/ARR genotype, although equally susceptible to experimental scrapie, have very little PrPSC in lymphoid tissues. The reasons for this finding and how it relates to disease susceptibility are under investigation. A major new project will also test whether resistant sheep are truly resistant or whether they actually become infected without showing clinical signs of disease. Such silent carriers could help explain how scrapie transfers between susceptible sheep and between flocks.
The route of infection with scrapie has been assumed to be via oral ingestion however it is not known exactly how the process occurs. We know from previous studies that the lamb at around the time of birth is highly susceptible to infection and that this susceptibility deceases with age. We are currently investigating the rates of transmission of scrapie between mother and lamb and will progress into a study of the lamb gut which undergoes considerable changes in early life as it matures, firstly absorbing nutrients from milk, then weaning on to grass at which point rumination develops. These structural physiological events may control the rate of initiation of infection following ingestion of scrapie and its transfer from the gut lumen into the body of the animal.
This lab has amassed considerable information relating to the characteristics of TSE strains but we are also interested in what happens to strains when they occur as a mixed infection in sheep. Do the strains remain separate in the mixture or is a new strain created? In a linked project we are also investigating the genetics and pathogenesis of newly identified naturally occurring TSE strains, for example, the recently described Atypical Scrapie. It is not known whether Atypical Scrapie is really a new disease or not, however the institute has an extensive sheep tissue archive and we are now searching for previously undiscovered Atypical Scrapie in these samples which date back to the 1960s.