Protease-resistant prion protein in brain and lymphoid organs of sheep within a naturally scrapie-infected flock

The hallmark of transmissible spongiform encephalopathies (TSE), such as sc rapie in sheep, is the accumulation in tissues of an insoluble and protease resistant form (PrPres) of the cellular prion protein. In this study, we e valuated whether the diversity in both the clinical pattern and the PrP gen otypes of scrapied sheep from the same flock was connected with different l evels and/or glycoform patterns of the PrPres in the brain and lymphoid org ans of the animals. Whereas the PrPres levels in spleen, lymph nodes and to nsils from sheep of different PrP genotypes and clinical status appeared co mparable, they were highly variable in brain, particularly in the brain ste m and the cerebellum PrPres was only detected in sheep bearing at least one VRQ allele, including three asymptomatic sheep and the highest PrPres load was found in the cerebellum of VRQ/VRQ animals. All together, levels of Pr Pres in brain did not necessarily correlate with the severity of the clinic al disease but might depend on the PUP genotype of the animals. Different b rain regions from a given sheep displayed a similar glycopattern of PrPres, whereas the apparent molecular sizes of the unglycosylated and diglycosyla ted forms of the protein differed between brain and lymphoid tissues. We di d not find any notifiable differences in the glycopattern of PrPres in brai n from sheep of different PrP genotypes or different clinical status and th is PrPres glycotype was also similar to that found in brain from four cattl e BSE. (C) 2000 Academic Press.