Control of natural resistance to salmonella typhimurium and leishmania donovani in mice by closely linked but distinct genetic loci

Inbred strains of mice vary in their sensitivity to infection with both Salmonella typhimurium^1,2 and Leishmania donovani³. In both cases, this differential susceptibility is genetically controlled. Resistance to the intracellularparasite L. donovani is determined by a single locus on chromosome 1, designated Lsh (ref. 4). The primary regulator of resistance to S. typhimurium is a single, dominant autosomal gene, named Ity (for immunity to typhimurium)⁵, and it has also been recently mapped to chromosome 1 (ref. 6). In addition, two other genetic loci regulate resistance to S. typhimurium in mice. These genes, Lps^d and xid, are mutant alleles that render C3H/HeJ and CBA/N mice, respectively, salmonella susceptible^7,8. Both Bradley and his colleagues^3,4, and Plant and Glynn^2,6, noted similar patterns of resistance or susceptibility of inbred strains of mice to L. donovani and S. typhimurium, and therefore suggested that Lsh and Ity might be the same gene. Mapping of both genes to the same region of chromosome 1 supported this hypothesis but no linkage studies have been used to test it. Since recombinant inbred (RI) mouse strains are, in effect, permanent segregant populations⁹, they are ideal for determining linkage between resistance genes to two different pathogens. Therefore, we determined the S. typhimurium susceptibility of five sets of RI mouse strains that had been previously typed for Lsh⁴ and conclude that Lsh and Ity are closely linked but distinct genetic Human B lymphocytes areloci.