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

Host 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 B10.AKM/Ola 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 x C57BL/6J F1 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 F1 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.