Identification of genetic loci controlling bacterial clearance in experimental Salmonella enteritidis infection: an unexpected role of Nramp1 (Slc11a1) in the persistence of infection in mice

Abstract

The Gram-negative

Genetic regulation of host responses to Salmonella infection in mice

“…Now the future of mouse genetics in the study of host resistance to Salmonella and other infections is moving toward the identification of inbred mouse strains that show a complex mode of inheritance to specific pathogens for QTL gene identification. 19,20,[153][154][155][156][157][158][159][160] Dissection of the complex host response to Salmonella infection combined with the complete mouse genome sequence will contribute further to our understanding of the genetic control of host immunity.…”

“…19,20 The wild-derived inbred mice, Mus musculus molossinus (MOLF/Ei), were initially found to be extremely susceptible to Salmonella Typhimurium with survival time comparable to the survival time of C57BL/6J (Nramp1 s ). Subsequently, linkage analysis using 252(C57BL/6J Â MOLF/Ei)F2 allowed the mapping of two QTLs, which significantly affect survival time following lethal infection with Salmonella Typhimurium.…”

“…19 Two strains, C57BL/6J (Nramp s ) and 129S6/ SvEvTac (Nramp1 r ), were characterized according to their ability to clear Salmonella Enteritidis from the spleen. 129S6/SvEvTac mice were found to have markedly impaired ability to clear the parasite when compared to C57BL/6J.…”

“…More recently, the development of novel models of infection together with quantitative trait mapping has identified additional host susceptibility loci. 19,20 This review will highlight key studies that led to the discovery of major Salmonella resistance genes in mice using different approaches including the generation of congenic mouse strains, positional cloning of spontaneous mouse mutations associated with susceptibility to Salmonella infection, targeted disruption of candidate genes and quantitative trait loci (QTL) mapping (Figure 1). …”

Looking back and looking forward

“…These included evidence for and mapping of multiple genes controlling IgE levels in Leishmania major infected mice 26 as well as a study implicating SLC11A1 (NRAMP1) in the persistence of Salmonella infection in mice. 27 Another provocative study linked a gp130 gene 'knock-in' with susceptibility to Listeria infection. 28 This gene, which is a critical subunit of IL-6 family genes, is within the critical region for a QTL identified in other studies of Listeria mouse infection.…”