Genetic analysis of susceptibility to isoniazid-induced seizures in mice

Four sets of recombinant inbred lines of mice have been used to analyze genetic differences in acute toxicity of the drug, isonicotinic acid hydrazide. Standard inbred strains, their F(1) hybrids and recombinant inbred strains were all challenged with a single dose of the drug. The percent mortality of the different groups was analyzed to estimate heritability and the number of genes affecting resistance. The data indicated that resistance factors were dominant, heritability was moderate (.25-.37), and more than one gene was involved in each of four different sets of recombinant inbred lines. Possible approaches for identifying and mapping individual genes affecting resistance are discussed.