Poster 36
Presenter: Jean Jaubert
Thursday, 4:00 – 6:00pm

Wild-derived Mus spretus strains : a resource for genetic dissection of resistance to Plague

Charlotte Leblanc^1,2, Charlène Blanchet^1,2, Elisabeth Carniel³, Christian Demeure³, Robert Gefferts⁴, Claudia Pommerenke⁴, Klaus Schughart⁴, Jean-Jacques Panthier^1,2, Xavier Montagutelli^1,2 and Jean Jaubert^1,2
1Institut Pasteur, Mouse Functional Genetics Unit, F-75015 Paris, France ²CNRS URA 2578, F-75015 Paris, FRANCE ³Institut Pasteur, Yersinia Unit, F-75015 Paris, France ⁴Department of Infection Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig, Germany

Plague is caused by the Gram-negative bacterium Yersinia pestis. Laboratory mice are susceptible to plague. We have recently described that wild-derived Mus spretus SEG/Pas mice were exceptionally resistant (90%) to the virulent CO92 wild-type strain of Y. pestis in an experimental model of bubonic plague. We screened other Mus spretus derived strains and identified the STF/Pas strain as susceptible. QTL mapping in an intercross between SEG resistant and STF susceptible strains led to the identification of two genomic intervals on chromosome 8. These QTLs are distinct from the three previously identified in a cross between SEG and C57BL/6J strains (Blanchet et al., 2011). Incipient-congenic (N5-N7) females carrying a heterozygous Chr8-SEG/STF fragment showed statistically higher survival rate after infection than homozygous Chr8-STF/STF female littermates. Macrophages are well recognized as being at the forefront of innate immune response to Y. pestis. We extracted peritoneal macrophages from both parental Mus spretus strains and incubated them ex vivo for 3 hours with Y. pestis. We also performed exome sequencing of both strains. Preliminary transcriptomic and exomic differences will be presented. Combination of QTL, exomic and transcriptomic datas should help in unravelling some of the mechanisms involved in resistance to plague.