Protease-resistant PrP deposition in brain and non-central nervous system tissues of a murine model of bovine spongiform encephalopathy.

Infectivity within the central nervous system has been demonstrated by the transmission of bovine spongiform encephalopathy (BSE) from affected cattle to inbred laboratory mice. Sedimentable, protease-resistant PrP (PrPSc) has also been extracted from BSE-affected cattle brain. Both infectivity and PrPSc have been reported in the lymphoreticular tissues of sheep and mice clinically and preclinically affected with scrapie. Neither infectivity nor PrPSc has yet been detected in non-neural tissues of naturally occurring, clinical cases of BSE in cattle. We have used a murine model of BSE (301V isolate in VM/Dk mice) to investigate when and where PrPSc accumulates. PrPSc was detected both in brain and in extraneural sites prior to the onset of clinical symptoms. This murine BSE model differs, however, in four important aspects from our previously published findings for murine scrapie models: (a) PrPSc was found relatively late into the incubation period; (b) after intracerebral inoculation, PrPSc was found in brain before it was found in other tissues; (c) no PrPSc was found in most of the spleens from clinically affected animals after intracerebral inoculation; and (d) even after intraperitoneal infection, PrPSc was detected in brain first.