Mouse lines which are congenic for , the major gene controlling scrapie incubation period, have been produced by selective breeding from the inbred C57BL( ) and VM( ) strains; the s7 allele of has been introduced into a VM background by 18 serial backcrosses, at each generation selecting on the basis of the incubation period with the ME7 scrapie strain. The characteristics of the disease produced by seven scrapie strains have been compared in and congenic mice and in the F cross between them. As previously found in non-congenic mice, each scrapie strain has a characteristic, precisely reproducible incubation period pattern in the three genotypes. The gene controls the incubation period for all scrapie strains tested but the direction of allelic action and the apparent dominance pattern differs between scrapie strains. Comparison with non-congenic mice shows that other genes also have a minor effect on incubation period. The distribution of vacuolar degeneration in the brain depends mainly on the scrapie strain but is also influenced by and other unspecified mouse genes. Restriction fragment length polymorphism analysis has already shown that the close linkage between and the gene encoding PrP has been maintained in the congenic lines, strengthening the possibility that PrP is the gene product. The present study confirms that scrapie strains carry information which is independent of the host but nevertheless suggests that host PrP protein interacts with this information to regulate the progression of the disease.


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