SCRAPIE STRAIN VARIATION AND MUTATION

There are many strains of scrapie, distinguishable by their disease ch aracteristics in genetically-defined mice. Numerous distinct strains h ave been isolated in the same mouse strain, indicating that scrapie ag ents have an informational molecule, independent of the host. Strain c haracteristics are stable on serial mouse passage under constant passa ging conditions. However, changes in the species or mouse genotype use d for passage may lead to changes in properties which are consistent w ith the selection of variants which replicate faster in the new host, rather than active modification of the agent by the host. The fact tha t this has been observed with biologically cloned strains is evidence for mutation in the scrapie agent. Transmissions to mice from natural scrapie and BSE suggest that strain variation exists in the field. The se findings have important implications when considering the molecular nature of the scrapie agent and the details of agent-host interaction s.