Primary isolation of the bovine spongiform encephalopathy agent in mice: agent definition based on a review of 150 transmissions.

In the epizootic of bovine spongiform encephalopathy (BSE) in Great Britain, the cattle in which a positive diagnosis was made numbered almost 180 000, but strain characterization was performed on only a very small sample of these cases. This report describes the results of BSE transmission to Prnp(a) mice from 150 transmission experiments at the Veterinary Laboratories Agency (VLA) over the last decade. These data, derived from a large sample of BSE-affected cattle, confirmed previous reports that show no evidence for diversity in BSE isolates. The agent was readily transmitted to mice, with a mean incubation period of 408 days in the RIII strain. Because the incubation period was related to the titre of the inoculum, it is not a reliable characteristic of strain type on primary isolation. Consistent neuropathological changes associated with infection by the BSE agent in RIII and C57Bl mice included focal vacuolation in the dorsal cochlear nuclei, vacuolation of the granule cell layer of the cerebellum, absence of lesions in the hippocampus and in the molecular layer of the cerebellum, and a fine particulate distribution of disease-specific PrP (demonstrated immunohistochemically), with few or no amyloid plaques. These features, together with the conventional lesion profile, will be of use in distinguishing the agents of BSE and scrapie in sheep.