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The Bcg gene story
1McGill Centre for the Study of Host Resistance, Montreal General Hospital, Quebec, Canada.
Immunobiology
|October 1, 1994
Summary
Researchers identified a single gene, Bcg, controlling susceptibility to mycobacterial infections in mice. This gene, natural resistance associated macrophage protein (Nramp), activates macrophages and may also influence tuberculosis resistance in humans.
Area of Science:
- Genetics
- Immunology
- Microbiology
Background:
- Genetic factors influencing mycobacterial infection susceptibility were suspected but poorly understood.
- Inherited mechanisms of susceptibility to intracellular parasites remained largely unknown.
Purpose of the Study:
- To identify the specific gene responsible for inherited resistance/susceptibility to mycobacterial infections.
- To elucidate the function and mechanism of this resistance gene.
Main Methods:
- Population genetics in mice to identify the Bcg gene.
- Recombinant inbred strains for gene mapping (chromosome 1).
- Physical mapping, gene identification (Nramp), and mutation analysis.
Main Results:
- Discovered a single dominant autosomal gene, Bcg, controlling susceptibility to mycobacteria and other intracellular parasites.
- Identified Nramp (natural resistance associated macrophage protein) as the candidate gene, expressed in macrophages.
- Linked a specific Nramp mutation (Gly-105 to Asp-105) to susceptibility (Bcgs).
- Found conserved homologous region on human chromosome 2q and significant linkage in a tuberculosis-affected family.
Conclusions:
- The Nramp gene is a strong candidate for the Bcg locus, mediating innate resistance through macrophage activation.
- Nramp likely plays a significant role in human tuberculosis susceptibility, representing a potential therapeutic target.