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Mus spretus SEG/Pas mice resist virulent Yersinia pestis, under multigenic control

Genes & Immunity volume 12, pages 23–30 (2011)Cite this article

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Abstract

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 102 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 107 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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Institut Pasteur, Mouse Functional Genetics Unit, Paris, France

    C Blanchet, J Jaubert, J-J Panthier & X Montagutelli

  2. CNRS, URA2578, Paris, France

    C Blanchet, J Jaubert, J-J Panthier & X Montagutelli

  3. Institut Pasteur, Yersinia Unit, Paris, France

    E Carniel & C Fayolle

  4. Institut Pasteur, Immunophysiology and Intracellular Parasitism Unit, Paris, France

    G Milon

  5. Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France

    M Szatanik

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  1. C Blanchet
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Correspondence to X Montagutelli.

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Blanchet, C., Jaubert, J., Carniel, E. et al. Mus spretus SEG/Pas mice resist virulent Yersinia pestis, under multigenic control. Genes Immun 12, 23–30 (2011). https://doi.org/10.1038/gene.2010.45

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