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

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 (Sinc sT) and VM (Sinc p7) 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 Sinc ~7 and Sinc p7 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.

The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological processes, demography of cattle and approaches to control by culling

“…There is much evidence to suggest the existence of distinct strains of the scrapie agent (Bruce et al 1991). These are distinguishable by their varied incubation periods and pathological indications in sheep and mice when host genetic background is controlled for.…”

Epidemiology and control of scrapie within a sheep flock

“…An important feature is the long mean incubation period of the disease (possibly two years or more). Evidence from experimental infections in mice indicates that the incubation period is a function of the route of infection and the infective dose, and that levels of abnormal PrP in the tissues (especially the central nervous system) increase from the time of ¢rst infection to the appearance of clinical signs (Bruce et al 1991). The mechanisms of natural transmission are incompletely understood.…”

“…It is not known whether`resistant' sheep cannot become infected or, by analogy with experimental infections of mice (Bruce et al 1991), whether the incubation period in these sheep is so long in relation to sheep life expectancy that clinical signs are never seen. In the latter case it is possible that`resistant' genotypes may act as carriers.…”

Rodent models for prion diseases

“…Mice and hamsters have since then been the most frequently used experimental animals in TSE research, due to their much easier maintenance and shorter incubation times, and because they allow to discriminate and characterise prion strains. Prion strains are characterised by their biological features (transmissibility, incubation times, brain spongiform lesion profiles, and the topology and quality of the PrP D depositions) following transmission to a panel of conventional inbred (RIII, C57Bl, VM) mice [14,17,38,42]. The same strain typing methodology has now also been applied to transgenic mice (e.g.…”