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

Abstract

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.

Identification of multiple quantitative trait loci linked to prion disease incubation period in mice

“…Previous reports suggested a QTL for incubation time on chromosome 17 within the H2 locus of the major histocompatibility complex, although this was not replicated by others or identified in our cross (18,34). However, challenge with different prion strains by different routes of inoculation and in other strains of mice may result in the segregation of alternative susceptibility genes.…”

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

“…The H-2D-linked effect, initially detected in congenic mouse strains infected with mouse-adapted CJD, has failed to be replicated by us or other investigators (33,34). Finally, although we do know that there are differences in the promoter region of the Prnp gene between the C57BL and RIII mouse strains, we do not detect any effect linked to the Prnp gene.…”

Scrapie strain-specific interactions with endogenous murine leukaemia virus.

“…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. It has been shown that different mouse strains within the same Sinc genotype, for example s(s(, can have different incubation periods for the same TSE strain (Kingsbury et al, 1983 ;Carp & Callahan, 1986 ;Dickinson & Outram, 1988 ;Mohri & Tateishi, 1989). Scrapie incubation period differences within the s(s( group of mice have been shown to be a function, in part, of H-2D locus (Kingsbury et al, 1983 ;Carp & Callahan, 1986).…”