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 n urturing environment influences variability in disease expression, natural resistance was found to be heritable and stably passed from parent to offsp ring. The bovine NRAMP1 gene was found to be one of the major candidate gen es involved the intracellular control of Salmonella dublin, Mycobacterium b ovis (BCC) and Brucella abortus in in vitro macrophage studies. In this mod el, the bovine NRAMP1 gene, the bovine homologue of a murine gene (Bcg) con trolling natural resistance to antigenically and taxonomically unrelated pa rasites, was identified to be influencing the in vivo resistant phenotype. Resistance-and susceptibility-associated alleles of bovine NRAMP1 were expr essed as transgenes under the regulatory control of the bovine NRAMP1 promo ter in a murine macrophage cell line (Bcg(3)). The 5' flanking region of bo vine NRAMP1, despite the lack of TATE and CAAT boxes, was found to have a f unctional promoter capable of driving the expression of a transgene in muri ne macrophages. A polymorphism within a microsatellite in the 3' UTR of bov ine NRAMP1 was found to critically affect the expression of the gene and th e capacity of transfected macrophages to control the in vitro replication o f Brucella but not Salmonella. Although genetic resistance to bacterial dis eases is often regulated by multiple genes controlling different processes of the host-pathogen interaction, the genetics of natural resistance is bei ng increasingly unraveled by identification and characterization of candida te genes, microsatellite markers, and comparative gene mapping to develop m ore practical methods of application.