1. Mus spretus SEG/Pas mice resist virulent Yersinia pestis, under multigenic control
- Author
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C. Fayolle, Elisabeth Carniel, Marek Szatanik, Geneviève Milon, Charlène Blanchet, Jean-Jacques Panthier, Xavier Montagutelli, Jean Jaubert, Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Yersinia, Institut Pasteur [Paris] (IP), Immunophysiologie et Parasitisme Intracellulaire, CB is a recipient of a DGA (Délégation Générale pour l’Armement) fellowship. This work was supported by a grant from Aventis Pharma (Sanofi-Aventis group) and Bayer Pharma as part of a multi-organism call for proposal. The Mouse functional Genetics Unit is supported by Merck Serono., We thank Jean-Louis Guénet for his constant interest and challenging discussions. We are grateful to Colin Crist for critical reading and suggestions on the paper, to Isabelle Lanctin for careful breeding of the SEG/Pas colony, and to the CNG (Centre National de Génotypage) for the SNP genotyping of BC mice., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]
- Subjects
Male ,Yersinia pestis ,Mus spretus ,Quantitative Trait Loci ,Immunology ,MESH: Yersinia pestis ,Virulence ,Quantitative trait locus ,Mice ,03 medical and health sciences ,Species Specificity ,Genetics ,Animals ,MESH: Species Specificity ,MESH: Animals ,Allele ,MESH: Mice ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,biology ,030306 microbiology ,Wild type ,biology.organism_classification ,Phenotype ,Immunity, Innate ,MESH: Male ,MESH: Quantitative Trait Loci ,3. Good health ,Backcrossing ,Female ,MESH: Immunity, Innate ,MESH: Female - Abstract
International audience; Laboratory mice are well known to be highly susceptible to virulent strains of Yersinia pestis in experimental models of bubonic plague. We have found that Mus spretus-derived SEG/Pas (SEG) mice are exceptionally resistant to virulent CO92 and 6/69 wild type strains. Upon subcutaneous injection of 10(2) colony-forming units (CFU), 90% of females and 68% of males survived, compared with only an 8% survival rate for both male and female C57BL/6 mice. Furthermore, half of the SEG mice survived a challenge of up to 10(7) CFU. The time required for mortality was similar between B6 and SEG, suggesting that survival is dependent on early rather than late processes. The analysis of 322 backcross mice identified three significant quantitative trait loci (QTLs) on chromosomes 3, 4 and 6, with dominant SEG protective alleles. Each QTL increased the survival rate by approximately 20%. The three QTLs function additively, thereby accounting for 67% of the difference between the parental phenotypes. Mice heterozygous for the three QTLs were just as resistant as SEG mice to Y. pestis challenge. The SEG strain therefore offers an invaluable opportunity to unravel mechanisms and underlying genetic factors of resistance against Y. pestis infection.
- Published
- 2011