Resistance to Salmonellosis in the Chicken Is Linked toNRAMP1and TNC

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Abstract
Natural resistance to infection withSalmonella typhimuriumin mice is controlled by two major loci,BcgandLps,located on mouse chromosomes 1 and 4, respectively. BothBcgandLpsexert pleiotropic effects and contribute to cytostatic/cytocidal activities of the macrophage.Bcgencodes for a membrane phosphoglycoprotein designatedNramp1(natural resistance-associated macrophage protein 1), which belongs to an ancient family of membrane proteins.Lpshas not been cloned yet, but its location on mouse chromosome 4 has been refined for positional cloning. As in mice, chicken inbred lines differ in their susceptibility to infection withSalmonella typhimurium.We have tested the candidacy of the chicken homologs ofNramp1andTnc(a locus closely linked toLps), in the differential resistance of chicken inbred lines to infection withS. typhimurium.We have first analyzed six inbred chicken lines ofSalmonella-resistant orSalmonella-susceptible phenotypes for the presence of nucleotide sequence variations within the coding portion ofNRAMP1.We have identified 11 sequence variations withinNRAMP1in the chicken inbred lines tested: 10 of these represented either silent mutations or conservative changes. However, one G → A substitution at nucleotide 696 resulted in the nonconservative replacement of Arg223to Gln223within the predicted TM5-6 region. This allelic variant was specific to the susceptible line C and not observed in any of the resistant strains. To investigate the effect ofNRAMP1andTNCon resistance to infection withS. typhimurium,425 (W1 × C)F1 × C chicken progeny were examined during a period of 15 days postinfection. Together,NRAMP1andTNCexplain 33% of the early differential resistance to infection withS. typhimuriumof parental lines C and W1. Our data established that resistance to infection withS. typhimuriumin chickens is inherited as a complex trait and that comparative mapping has proven to be useful to identifySalmonella-resistance genes in the chicken.