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Identification de facteurs génétiques contrôlant la résistance de lignées de souris consanguines à une infection expérimentale par Yersinia pestis, l'agent de la peste

Abstract : Plague is a zoonotic disease affecting mainly rodents and accidentally humans. The etiologic agent of bubonic and pneumonic plague is the Gram-negative bacterium Yersinia pestis. The mechanisms by which the host is able or not to resist the infection are poorly understood. We have shown that some mouse inbred strains, like C57BL/6J, die after the subcutaneous injection of 100 bacteria of a virulent strain (CO92), while others, like SEG/Pas, derived from Mus spretus, survive. A backcross between these two strains led to identification, on chromosomes 3, 4, and 6, of three QTL controlling survival rate. The first two were found only in females, while the chromosome 6 QTL was also found in males. Congenic mice carrying the SEG chromosome 6 in a C57BL/6J background were produced. After infection, they die in the same proportion as C57BL/6, but somewhat later. Bi- and tri-congenic strains are under production to assess the effect of other QTLs. We have tested a collection of 55 interspecific recombinant congenic strains between C57BL/6J and SEG/Pas. Several strains significantly differed from C57BL/6 in survival rate or time to death. The analysis of strain 120G, which dies earlier than C57BL/6J, suggests that the proximal region of chromosome 6 would be responsible for this phenotype. Altogether, our data show that genetic control of resistance to plague in SEG/Pas mice is complex, and we have identified several genomic regions which play an important role in this phenotype.
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Submitted on : Thursday, July 7, 2011 - 11:24:49 AM
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Charlène Blanchet. Identification de facteurs génétiques contrôlant la résistance de lignées de souris consanguines à une infection expérimentale par Yersinia pestis, l'agent de la peste. Génétique. AgroParisTech, 2009. Français. ⟨NNT : 2009AGPT0060⟩. ⟨pastel-00606835⟩

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