International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 12 - IDENTIFICATION OF GENETIC LOCI CONTROLLING SALMONELLA ENTERITIDIS CLEARANCE: AN UNEXPECTED ROLE OF NRAMP1 IN THE PERSISTENCE OF INFECTION

Miss Judith Caron
McGill University
Center for the Study of Host Resistance
Montreal General Hospital
1650 Cedar Avenue, Room L11-144
Montreal (Quebec) H3G 1A4
Canada

Co-Authors:  Laroche L, Skamene E, Loredo-Osti J, Morgan J, and Malo D
Institution:   Center for the Study of Host Resistance, McGill University  

Identification of genetic loci controlling salmonella enteritidis clearance: an unexpected role of nramp1 in the persistence of infection

Salmonella ssp. cause a spectrum of diseases in humans. We have developed a novel mouse model to study the contribution of genetic factors to the susceptibility of 129/SvJ and C57BL/6J mice to S. enteritidis during the late phase of infection. C57BL/6J mice cleared sublethal inoculum of S. enteritidis  from their spleen, whereas 129/SvJ mice presented high bacterial counts. A genome scan on  F2 hybrids identified a locus strongly linked with the disease susceptibility in 129/SvJ mice (designated Ses1) at D1Mcg5 with a LOD score of 9.9. Four other regions linked to susceptibility were also found (Ses2 to Ses5) at D1Mit123, D1Mit495, D7Mit62 and D15Mit29 with LOD scores of 4.3, 4.3, 4.0 and 3.4, respectively. Our results suggest that the bacterial clearance effects associated to all loci but D1Mit123 were greater in females. Linkage to Ses2 was detected only in males. The candidacy of Nramp1 as being the gene underlying Ses1 was evaluated because of its map position, its known role in innate immunity during S. typhimurium infection and the existence of a functional polymorphism between 129/SvJ and C57BL/6J mice. Analysis of the disease phenotype in mice carrying a null allele at Nramp1 showed that these mice have significantly lower spleen bacterial load compared to 129/SvJ, strongly suggesting a role for Nramp1 in controlling S. enteritidis clearance during the late phase of infection.


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