The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis

TLDR

The study confirms that scrapie strains carry strain‑specific information independent of the host, yet host PrP protein interacts with this information to regulate disease progression. The authors generated Sinc‑congenic mouse lines via 18 backcrosses and compared disease characteristics of seven scrapie strains across Sincs7, Sincp7, and their F1 hybrids. Each of the seven scrapie strains displayed a distinct, reproducible incubation period pattern controlled by the Sinc gene, with allelic action and dominance differing among strains and minor effects from other genes; strain‑dependent vacuolar degeneration was also influenced by Sinc and additional genes, and RFLP analysis linked Sinc to the PrP gene, supporting the view that strain‑specific information is host‑independent but modulated by host PrP.

Abstract

Mouse lines which are congenic for Sinc, the major gene controlling scrapie incubation period, have been produced by selective breeding from the inbred C57BL(Sincs7) and VM(Sincp7) strains; the s7 allele of Sinc 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 Sincs7 and Sincp7 congenic mice and in the F1 cross between them. As previously found in non-congenic mice, each scrapie strain has a characteristic, precisely reproducible incubation period pattern in the three Sinc genotypes. The Sinc 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 Sinc and other unspecified mouse genes. Restriction fragment length polymorphism analysis has already shown that the close linkage between Sinc and the gene encoding PrP has been maintained in the Sinc congenic lines, strengthening the possibility that PrP is the Sinc 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.