International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

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POSTER 164 - GENETICS OF HOST RESISTANCE TO CHRONIC SALMONELLA INFECTION IN MICE

Caron J
Department of Human Genetics

Co-Authors: 1) Loredo-Osti J C, 1,2) Morgan K, 1,2,3) Malo D
Institutions: 1) Department of Human Genetics, 2) Center for the Study of Host Resistance, 3) Department of Medicine, McGill University

The Gram-negative bacteria, Salmonella, cause a broad spectrum of clinical diseases in humans. We have developed a model to study the contribution of genes to the susceptibility of 129sv and C57BL/6J mice to Salmonella enteritidis during the late phase of infection. A genome scan performed on 302 (C57BL/6J x 129sv) F2 progeny identified two highly significant linkages on chromosomes 1 (Ses1) and 7 ( Ses2) with respective LOD scores of 9.9 (p=1.4x10^-11) at D1Mcg5 and 4.0 (p=1.9x10^-5) at D7Mit62 and one highly suggestive QTL on chromosomes 15 (Ses3) with a LOD score 3.4 (p=1.2x10^-4). All QTLs were associated with disease susceptibility in 129sv mice, and their estimated effects on the bacterial clearance were greater in females. Using a model of three loci, with interaction between Ses1 and Ses2 and sex as a covariate, the three QTLs explained 32% of the phenotypic variance. The candidacy of Slc11a1 as the gene for Ses1 was evaluated using mice carrying a null allele at Slc11a1 (129sv-Slc11a1^tm1Mcg). These mice had a significantly lower spleen bacterial load compared to the wild-type 129sv mice, strongly suggesting the involvement of Slc11a1 in controlling Salmonella enteritidis clearance during the late phase of infection. The independent and combined contribution of Ses1, Ses2 and Ses3 to disease susceptibility is being investigated using congenic mice. The identification of the genes involved in our model is being approached using microarray technology combined with candidate gene and knockout approaches.