Substrains of 129 mice are resistant to Yersinia pestis KIM5: implications for interleukin-10-deficient mice.

Interleukin-10 (IL-10)-deficient mice are resistant to several pathogens, including Yersinia pestis. Surprisingly, we observed that heterozygous IL-10(+/-) mice also survive high-dose intravenous infection with Y. pestis KIM5 (Pgm(-)). Analysis of commercial IL-10(-/-) mice revealed that at least 30 cM of genomic DNA from the original 129 strain remains, including a functional Slc11a1 (Nramp1) gene. Interestingly, two substrains of 129 mice were resistant to high-dose Y. pestis KIM5. Resistance does not appear to be recessive, as F(1) mice (C57BL/6J x 129) also survived a high-dose challenge. A QTL-based genetic scan of chromosome 1 with 35 infected F(1) backcrossed mice revealed that resistance to KIM5 maps to a region near IL-10. Two novel IL-10(+/+) mouse strains which each possess most of the original 30-cM stretch of 129 DNA maintained resistance to high-dose infection with Y. pestis KIM5 even in a heterozygous state. Conversely, a novel IL-10(-/-) mouse strain in which most of the 129 DNA has been crossed out exhibited intermediate resistance to KIM5, while the corresponding IL-10(+/-) strain was completely susceptible. Taken together, these results demonstrate that 129-derived genomic DNA near IL-10 confers resistance to Yersinia pestis KIM5 and contributes to the observed resistance of IL-10(-/-) mice.