Host-genotype and agent effects in scrapie incubation: Change in allelic interaction with different strains of agent

SUMMARYHost genetic control of the incubation period of Creutzfeldt-Jakob disease (CJD) was studied using various inbred strains of mice, including B10 congenic strains. Various incubation periods were found in mice injected either intracerebrally or intraperitoneally with the Fukuoka 1 strain of the CJD agent; NZW/Sea and A/JJms had the shortest, and BI0.AKM/OIa and C57BL/6J the longest, incubation periods. Length of the CJD incubation period did not correlate with the genetic markers tested, i.e. the murine major histocompatibility (H-2) complex (which has previously been reported to be linked to a gene influencing CJD incubation period in mice), coat colour or sex genes. In NZW/Sea × C57BL/6J F 1 hybrid mice the CJD incubation periods were similar to that of the parent with the longest incubation period. Incubation periods of the backcross progeny from F1 and NZW/Sea were intermediate between those of the parental mice and had a unimodal distribution pattern. A similar observation was made on the progeny of the A/JJms x C57BL/6J mating. On the other hand, the length of incubation period for the NZW/Sea x B10. AKM/Ola F1 hybrid fell between those for the two parents and the NZW/Sea x A/JJms F~ hybrid had a significantly longer incubation period than those of the two parents. These results suggest that polygenes probably control the length of the CJD incubation period in mice.

Section: × C57bl/6j)supporting

confidence: 90%

Host Genetic Control of Incubation Periods of Creutzfeldt-Jakob Disease in Mice

Mohri

Tateishi

1989

“…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. The 22A scrapie strain has the opposite pattern with a short incubation period in p(p( mice and a long incubation period in s(s( mice (Dickinson & Meikle, 1971). Comparison of incubation periods for ME7, 139A and 22L versus that of 22A clearly establishes that the mouse strains used in these studies have the s(s( genotype.…”

Section: Discussionmentioning

confidence: 70%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Analyses of the interaction between TSE agents and host is accomplished most effectively using the archetype of these diseases, scrapie. One of the key advantages of the scrapie model system is the availability of numerous, well-characterized strains which produce distinctive effects (Dickinson & Meikle, 1971 ;Bruce et al, 1976 ;Dickinson & Fraser, 1979 ;Carp et al, 1984 ;Kim et al, 1987 ;Carp & Rubenstein, 1991). An additional advantage in the mouseadapted scrapie strains is gained by the use of inbred mouse strains.…”

Section: Introductionmentioning

confidence: 99%

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Scrapie strain-specific interactions with endogenous murine leukaemia virus.

Carp¹,

Meeker²,

Caruso³

et al. 1999

The finding that a senescence-accelerated mouse (SAMP8) shows early brain ageing, with histopathological changes resembling those seen in scrapie, combined with the discovery of high levels of endogenous murine leukaemia virus (MuLV) in brains of SAMP8 mice prompted us to examine the effect of scrapie infection on MuLV titres in this strain and in one of its progenitors, the AKR strain. Three scrapie strains (ME7, 22L and 139A) that had a comparatively short incubation period in SAMP8 and AKR mice caused an increase in brain MuLV titres that was scrapie strainspecific : in each mouse strain, the greatest effect was with 139A, and the least with ME7. The 22A scrapie strain, which has a long incubation period in SAMP8 mice, did not affect MuLV titres in brains of this mouse strain. Previous analyses of scrapie incubation periods in AKR, SAMP8 and another strain derived from an AKR cross (SAMR1) showed an inverse relationship between brain MuLV titres and scrapie incubation periods. This finding, combined with the effect of scrapie on MuLV titres, suggests an interaction between the scrapie infectious process and MuLV replication.

“…Passages from a single host into different species (Kimberlin & Walker, 1977, 1978Kimberlin et al, 1987Kimberlin et al, , 1989, or into mice with different Sinc genotypes (Dickinson & Outram, 1983), often yield scrapie agent populations with different characteristics. The passage lines were analysed for two parameters that are under genetic control of host and agent: incubation periods in mice of different Sinc genotypes (Dickinson & Meikle, 1971) and increase in weight during the preclinical phase of disease (Outram, 1972;Carp et al, 1984Carp et al, , 1989cKim et al, 1987 b). In the present study, initiation of lines from the same sheep in different Sinc genotypes led to differences in one or both parameters.…”

Section: Introductionmentioning

confidence: 99%

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

Carp

Callahan

1991

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.