Genetics of carbon tetrachloride-induced liver injury in mice. II. Multigenic regulation

Mice from many different congenic inbred strains were given an intramuscular injection of carbon tetrachloride (CCl₄) in olive oil to determine the genetic influences on induction of, and recovery from, liver damage. Liver and blood samples were taken at days 1, 4 and 7. The degree of necrosis and lymphoid infiltration appeared to be controlled, qualitatively and quantitatively, by both H-2-linked and Ah-linked genes. Strain differences were noted in the patterns of hepatocellular necrosis and the proportions of lymphoid, monocytic and other inflammatory cells which characterized the infiltrating population. Kinetic studies of F₁ hybrids from matings between the susceptible BALB/cJ male parent and the resistant SJL/J female parent suggested that two dominant genetic influences play a major role in liver necrosis and a second gene from SJL/J augments recovery. These results suggest, therefore, that the CCl₄-induced liver damage and subsequent recovery are under multigenic control by H-2, Ah and possibly other genes.