CHROMOSOME 1 LOCUS : A MAJOR REGULATOR OF NATURAL RESISTANCE TO INTRACELLULAR PATHOGENS

Abstract

Natural resistance to infection with several intracellular pathogens— both bacterial and protozoal—has recently been demonstrated to be under genetic control. The ability of genetically-resistant mouse strains to prevent growth, in the reticuloendothelial tissues, of Mycobacterium bovis (BCG) is controlled by a single, dominant, autosomal gene designated Bcg. In a study described in the chapter, mice of 17 inbred strains were infected intravenously with 10 4 CFU of M. bovis (BCG) and Bcg typed 3 weeks later as either resistant (r) or susceptible (s) according to the level of bacterial burden in their spleens. Because the strain survey and the analysis of recombinant inbred strains suggested a close linkage (or identity) of Bcg, Lsh, and Ity genes, a formal proof was sought by the examination of individual animals obtained from a segregating population for the distribution of the three phenotypes in question. Twenty-six backcross animals and the appropriate parental and F 1 hybrid controls were infected with BCG and they were splenectomized three weeks later for Bcg typing. The recent availability of mouse strains that are congenie except for the Bcg (Lsh, Ity) gene should greatly enhance the functional studies on the phenotypic expression of this gene.