TY - JOUR
T1 - Substrains of 129 mice are resistant to Yersinia pestis KIM5
T2 - Implications for interleukin-10-deficient mice
AU - Turner, Joshua K.
AU - Xu, John L.
AU - Tapping, Richard I.
PY - 2009/1
Y1 - 2009/1
N2 - 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 F1 mice (C57BL/6J x 129) also survived a high-dose challenge. A QTL-based genetic scan of chromosome 1 with 35 infected F1 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.
AB - 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 F1 mice (C57BL/6J x 129) also survived a high-dose challenge. A QTL-based genetic scan of chromosome 1 with 35 infected F1 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.
UR - http://www.scopus.com/inward/record.url?scp=58449095216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58449095216&partnerID=8YFLogxK
U2 - 10.1128/IAI.01057-08
DO - 10.1128/IAI.01057-08
M3 - Article
C2 - 18955473
AN - SCOPUS:58449095216
SN - 0019-9567
VL - 77
SP - 367
EP - 373
JO - Infection and immunity
JF - Infection and immunity
IS - 1
ER -