Genetic dissection of the ity3 locus identifies a role for ncf2 co-expression modules and suggests selp as a candidate gene underlying the ity3.2 locus.

[typhoid]

Typhoid fever and salmonellosis , which are caused by Salmonella typhi and typhimurium , respectively , are responsible for significant morbidity and mortality in both developed and developing countries . We model typhoid fever using mice infected with Salmonella typhimurium , which results in a systemic disease , whereby the outcome of infection is variable in different inbred strains of mice . This model recapitulates several clinical aspects of the human disease and allows the study of the host response to Salmonella typhimurium infection in vivo . Previous work in our laboratory has identified three loci (Ity , Ity 2 , and Ity 3 ) in the wild-derived MOLF /Ei mice influencing survival after infection with Salmonella typhimurium . Fine mapping of the Ity 3 locus indicated that two sub-loci contribute collectively to the susceptibility of B 6 .MOLF-Ity /Ity 3 congenic mice to Salmonella infection . In the current paper , we provided further evidence supporting a role for Ncf 2 (neutrophil cytosolic factor 2 a subunit of NADPH oxidase ) as the gene underlying the Ity 3 .1 sub-locus . Gene expression profiling indicated that the Ity 3 .1 sub-locus defined a global gene expression signature with networks articulated around Ncf 2 . Furthermore , based on differential expression and complementation analysis using Selp (selectin-P ) knock-out mice , Selp was identified as a strong candidate gene for the Ity 3 .2 sub-locus .

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typhoid

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