Variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep

Ten mouse-passaged scrapie lines were initiated from five sheep with clinical scrapie. Of the lines, five were initiated and passaged exclusively in mice with the s7s7 genotype and the remaining five lines were initiated in mice with the p7p7 genotype, with two of these lines subsequently being passaged exclusively in p7p7 mice and two being passaged mainly in p7p7 mice. Lines were passaged three or four times and two parameters were compared: incubation period and the induction of a weight increase during the preclinical period. Considerable variation in the incubation periods was found between the different passage lines at similar passage levels, with a range in s7s7 mice of 113 days to greater than 450 days and a range in p7p7 mice of 219 days to greater than 500 days. All of the lines passaged exclusively in s7s7 mice had shorter incubation periods in this mouse genotype than in p7p7 mice, whereas of the five lines initiated in p7p7 mice, two had shorter incubation periods in p7p7 mouse strains. C57BL mice were used as the indicator strain and most of the lines caused an increase in weight during the preclinical phase of disease compared to control mice injected with normal brain homogenates. For both parameters, incubation period and preclinical weight increase, differences were seen in lines that had identical passage histories, suggesting that an informational molecule separate from host genomic material must specify scrapie strain differences.