Bovine natural resistance macrophage protein 1 (NRAMP1) gene

Genetically based natural resistance to brucellosis provides an innovative strategy to reduce this major zoonotic disease of cattle. Even though the nurturing environment influences variability in disease expression, natural resistance was found to be heritable and stably passed from parent to offspring. The bovine NRAMP1 gene was found to be one of the major candidate genes involved the intracellular control of Salmonella dublin, Mycobacterium bovis (BCC) and Brucella abortus in in vitro macrophage studies. In this model, the bovine NRAMP1 gene, the bovine homologue of a murine gene (Bcg) controlling natural resistance to antigenically and taxonomically unrelated parasites, was identified to be influencing the in vivo resistant phenotype. Resistance-and susceptibility-associated alleles of bovine NRAMP1 were expressed as transgenes under the regulatory control of the bovine NRAMP1 promoter in a murine macrophage cell line (Bcg(3)). The 5' flanking region of bovine NRAMP1, despite the lack of TATE and CAAT boxes, was found to have a functional promoter capable of driving the expression of a transgene in murine macrophages. A polymorphism within a microsatellite in the 3' UTR of bovine NRAMP1 was found to critically affect the expression of the gene and the capacity of transfected macrophages to control the in vitro replication of Brucella but not Salmonella. Although genetic resistance to bacterial diseases is often regulated by multiple genes controlling different processes of the host-pathogen interaction, the genetics of natural resistance is being increasingly unraveled by identification and characterization of candidate genes, microsatellite markers, and comparative gene mapping to develop more practical methods of application.