Classic genetics of scrapie

Many years ago, observations of natural scrapie revealed differences in clinical manifestations and in the areas of the brain that showed the most intense histopathological changes. In experimental work with scrapie in mice two fundamental points were established in early studies: (1) A mouse gene, termed Sinc for scrapie incubation, affects the length of the incubation period. (2) In a single strain of mice, incubation periods of different "strains" of scrapie can differ by as much as 3-4 fold, e.g., the incubation period of the ME7 scrapie strain in C57BL mice is approximately 122 days, whereas the incubation period for the 22A strain is 360 days. From this "classic" beginning our knowledge about the parameters influenced by genetic characteristics of both host and agent have expanded. In a number of instances, initial examination of an aspect of host-agent interaction has subsequently revealed surprising influences of informational molecules from both host and agent. A partial list of the parameters under genetic control follows: (1) The extent of vacuolation in various regions of the brain; (2) The quantity of amyloid plaques in the brain; (3) The occurrence of increased weight in the preclinical phase of disease; (4) The development of aberrant glucose tolerance; (5) The area of the brain which yields the shortest incubation period after stereotaxic injection; and (6) The physical-chemical and immunological characteristics of scrapie associated fibrils. In several well documented instances differences between scrapie strains were evident after repeated passages of the strains in the same host strain.(ABSTRACT TRUNCATED AT 250 WORDS)