Evidence inconsistent with a role for the Bcg gene (Nramp1) in resistance of mice to infection with virulent Mycobacterium tuberculosis

The superior resistance of some strains of mice over others to infection with certain intracellular pathogens, including the vaccine strain of Mycobacterium bovis, bacillus Calmette Guerin (BCG), is determined by a gene associated with a small segment of chromosome 1 designated the Ity/Lsh/Bcg locus, referred to here as the Bcg locus. DBA/2 mice containing the dominant resistant allele of the Bcg gene (Bcg(r)), major histocompatibility complex-compatible BALB/c mice containing the recessive susceptible allele (Bcg(s)), and congenic C.D2-N20 Bcg(r), which are genetically the same as BALB/c mice except for possessing a small piece of DBA/2 chromosome 1 containing the Bcg locus, were used to determine whether the Bcg gene determines resistance to infection with the virulent H37Rv strain of Mycobacterium tuberculosis (Mtb). According to the survival times of Bcg(r) and Bcg(s) mice infected via either the intravenous or respiratory route, Brg(r) mice proved much less, rather than more, resistant to Mtb infection than Bcg(s) mice. Shorter survival times of Bcg(r) mice were associated with an inferior capacity to control Mtb growth in their lungs and to retard the development of Mtb-induced pathology in this organ. Resistance to Mtb infection was a dominant trait in the F1 progeny of Bcg(r) and Bcg(s) mice. The results show that resistance to Mtb is not determined by the resistance allele of the Bcg gene nor by the recently isolated candidate Bcg gene Nramp1, located in the Bcg locus.