International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 182 - FINE MAPPING OF QTL'S UNDERLYING IMMUNITY TO SALMONELLA TYPHIMURIUM IN WILD-STRAIN MICE

Sancho V
McGill University

Co-Authors: Lacroix G, Malo D
Institutions: McGill University

Salmonella Typhimurium is a ubiquitous pathogen that infects both mice and humans, manifesting typhoid-like systemic fever in mice and salmonellosis in humans. Previous studies have shown that the wild-derived inbred mouse Mus musculus molossinus (MOLF/Ei) are extremely susceptible to infection by Salmonella Typhimurium despite the presence of functional alleles at known Salmonella-susceptibility loci such as Slc11a1 (Nramp1) and Tlr4. Crosses between C57BL/6J and MOLF/Ei has lead to the identification of two novel QTLs, Ity2 and Ity3, that influence survival time during Salmonella Typhimurium infection. Ity2 is a resistance locus on chromosome 11 located between D11Mit79 and D11Mit13, whereas Ity3 is a susceptibility locus on chromosome 1 located approximately 25cM distal to Slc11a1. We have developed congenic strains to carry out fine mapping of Ity2 (B6.MOLF-Slc11a1Gly169Ity2) and Ity3 (B6.MOLF-Slc11a1Gly169Ity3). Four Ity2 congenic lines were challenged with Salmonella Typhimurium and resistance to infection was measured using survival analysis. This analysis suggests that the effect of this large QTL is explained by at least two distinct genes. We are using haplotype mapping to reduce the number of potential candidate genes within the QTL intervals. The candidacy of genes such as Ncf2 and Ikbke for Ity3, and Irf-1 for Ity2 was assessed via sequence, expression and functional analyses.


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