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

Abstract

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.

Scrapie strain-specific interactions with endogenous murine leukaemia virus.

“…The inverse relationship between MuLV titres and scrapie incubation periods is seen also with 22A, in which the SAMP8 incubation period was 422 days, whereas the incubation period in SAMR1 was 505 days. In addition, a recently developed strain (C603) (Carp & Callahan, 1991) had incubation periods of 215p2 days in SAMP8 mice and 270p11 days in SAMR1 mice.…”

“…The scrapie incubation period gene, Sinc (Dickinson & Meikle, 1971 ;Dickinson & Fraser, 1979 ;Carp & Callahan, 1991) [also referred to as Prn-1 (Carlson et al, 1986)], is the mouse gene that has a major influence on the length of the scrapie incubation period. Mice with the s(s( allele have a comparatively short incubation period for scrapie strains such as ME7, 139A and 22L, whereas mice with the p(p( allele have a long incubation period for these scrapie strains.…”

Prion agent diversity and species barrier

“…The potential scrapie strain diversity in the USA (five isolates studied, [46]) and Japan (eight sources, [97]) has also been examined by similar methods. Diversified phenotypic traits were observed after transmission to mice, suggesting the existence of distinct strains.…”

“…This includes the CH1641 strain, passaged on this sheep genetic background [74]. Conventional inbred mouse lines are also refractory to isolates from atypical cases [38,119].The potential scrapie strain diversity in the USA (five isolates studied, [46]) and Japan (eight sources, [97]) has also been examined by similar methods. Diversified phenotypic traits were observed after transmission to mice, suggesting the existence of distinct strains.…”

Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.

“…Later, priori isolates, or strains, were studied in mice on the basis of incubation time measurements and neuropathologic changes Dickinson and Meikle 1971;Bruce and Dickinson 1987;Carp and Callahan 1991). Although the use of Prn-p a and Prn-p b strains of mice unknowingly complicated the study of distinct scrapie isolates (Westaway et al 1987;Carlson et al 1989), the existence of a limited number of isolates with distinct properties based on both incubation times and neuropathologic lesion profiles seems firmly established (Bruce et al 1991).…”