title: Pyruvate kinase deficiency confers susceptibility to Salmonella typhimurium infection in mice.
abstract: The mouse response to acute Salmonella typhimurium infection is complex, and it is under the influence of several genes, as well as environmental factors. In a previous study, we identified two novel Salmonella susceptibility loci, Ity4 and Ity5, in a (AcB61 x 129S6)F2 cross. The peak logarithm of odds score associated with Ity4 maps to the region of the liver and red blood cell (RBC)-specific pyruvate kinase (Pklr) gene, which was previously shown to be mutated in AcB61. During Plasmodium chabaudi infection, the Pklr mutation protects the mice against this parasite, as indicated by improved survival and lower peak parasitemia. Given that RBC defects have previously been associated with resistance to malaria and susceptibility to Salmonella, we hypothesized that Pklr is the gene underlying Ity4 and that it confers susceptibility to acute S. typhimurium infection in mice. Using a fine mapping approach combined with complementation studies, comparative studies, and functional analysis, we show that Pklr is the gene underlying Ity4 and that it confers susceptibility to acute S. typhimurium infection in mice through its effect on the RBC turnover and iron metabolism.
authors.affiliation: Department of Human Genetics, McGill University Health Center, Montréal, Québec, H3G 1A4, Canada.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Roy
authors.forename: Noémie
authors.initials: N
authors.lastname: Riendeau
authors.forename: Christian
authors.initials: C
authors.lastname: Bédard
authors.forename: Pierre
authors.initials: P
authors.lastname: Hélie
authors.forename: Gundula
authors.initials: G
authors.lastname: Min-Oo
authors.forename: Karine
authors.initials: K
authors.lastname: Turcotte
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
authors.forename: François
authors.initials: F
authors.lastname: Canonne-Hergaux
authors.forename: Danielle
authors.initials: D
authors.lastname: Malo
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D020022:Genetic Predisposition to Disease; D008126:Lod Score; D051379:Mice; D017354:Point Mutation; D011770:Pyruvate Kinase / Q000172:deficiency* / Q000235:genetics*; D012480:Salmonella Infections / Q000235:genetics*; D012486:Salmonella typhimurium / Q000472:pathogenicity*
chemical_list: D011770:Pyruvate Kinase