Histocompatibility-linked Genetic Control of Disease Susceptibility

Acute necrotizing inflammatory disease after intracerebral injection of LCM virus is largely dependent on the host immune response to the virus and is controlled, in part, by a dominant gene which is closely linked to the H-2 locus. The F(1) hybrid (H-2(q/k)) from mating a susceptible SWR/J mouse (H-2(q/q)) to a resistant C3H/HeJ mouse (H-2(k/k)) is susceptible to LCM virus disease. When such hybrids (H-2(q/k)) are backcrossed to susceptible parents (H-2(q/q)), all F(2) offspring (H-2(q/q), H-2(q/k)) are highly susceptible. In contrast, hybrid (H-2(q/k)) backcross to resistant parents (H-2(k/k)) results in half of the F(2) offspring being susceptible (H-2(q/k)) while the other half are resistant (H-2(k/k)). Similarly, in congenic H-2(q/q) and H-2(k/k) mice, H-2(q/q) mice are relatively susceptible to acute LCM disease, whereas H-2(k/k) are resistant.