Functionally distinct regions of the locus control IgE or IFNγ level in addition to skin lesions.

Leishmaniasis, a disease caused by parasites of spp., endangers more than 1 billion people living in endemic countries and has three clinical forms: cutaneous, mucocutaneous, and visceral. Understanding of individual differences in susceptibility to infection and heterogeneity of its pathology is largely lacking. Different mouse strains show a broad and heterogeneous range of disease manifestations such as skin lesions, splenomegaly, hepatomegaly, and increased serum levels of immunoglobulin E and several cytokines. Genome-wide mapping of these strain differences detected more than 30 quantitative trait loci (QTLs) that control the response to . Some control different combinations of disease manifestations, but the nature of this heterogeneity is not yet clear. In this study, we analyzed the locus originally mapped in the strain CcS-9 which carries 12.5% of the genome of the resistant strain STS on the genetic background of the susceptible strain BALB/c. For this analysis, we used the advanced intercross line K3FV between the strains BALB/c and STS. We confirmed the previously detected loci , , , and and performed genetic dissection of the effects of on chromosome 11. We prepared the interval-specific recombinant strains 6232HS1 and 6229FUD, carrying two STS-derived segments comprising the peak linkage of whose lengths were 6.32 and 17.4 Mbp, respectively, and analyzed their response to infection. These experiments revealed at least two linked but functionally distinct chromosomal regions controlling IFNγ response and IgE response, respectively, in addition to the control of skin lesions. Bioinformatics and expression analysis identified the potential candidate gene . This finding further clarifies the genetic organization of factors relevant to understanding the differences in the individual risk of disease.