THE HOST-RESISTANCE LOCUS BCG IS TIGHTLY LINKED TO A GROUP OF CYTOSKELETON-ASSOCIATED PROTEIN GENES THAT INCLUDE VILLIN AND DESMIN

In the mouse, innate resistance or susceptibility to infection with a group of unrelated intracellular parasites which includes, Mycobacteria, Salmonella, and Leishmania is determined by the expression of a single dominant autosomal gene designated Bcg located on the proximal portion of chromosome 1. The gene is expressed at the level of the mature tissue macrophage and influences its capacity to restrict intracellular proliferation of the parasites. We have used restriction fragment length polymorphism analysis in segregating populations of inter- and intraspecific backcross mice and in recombinant inbred strains to position four new marker genes, trasition protein 1 (Tp-1), desmin (Des), the α subunit of inhibin (Inha), and retinal S-antigen (Sag), in the vicinity of the host resistance locus, Bcg. The gene order for Tp-1, Des, Inha, and Sag was established in an eight-point testcross with respect to anchor loci previously assigned to that portion of mouse chromosome 1 and was found to be centromere-Fn-1-Tp-1-(Vil,Bcg)-Des-Inha-Akp-3-Acrg-Sag. Two of these new marker genes were found very tightly linked to Bcg: Des was located 0.3 ± 0.3 cM distal from (Vil,Bcg) and 0.3 ± 0.3 cM proximal to Inha. Tp-1 mapped 0.8 ± 0.5 cM proximal and Sag 12.8 ± 1.7 cM distal to (Vil,Bcg). Tp-1, Des, Inha, and Sag all fall within a large mouse chromosome 1 segment homologous with the telomeric region of the long arm of human chromosome 2 (2q). Our findings indicate that the two closest markers to the host resistance locus, Bcg, encode cytoskeleton-associated proteins which are capable of interaction with actin filaments. © 1991.