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Infection and Immunity, January 2009, p. 367-373, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01057-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Substrains of 129 Mice Are Resistant to Yersinia pestis KIM5: Implications for Interleukin-10-Deficient Mice{triangledown}

Joshua K. Turner,1 John L. Xu,1 and Richard I. Tapping1,2*

Department of Microbiology,1 College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 618012

Received 25 August 2008/ Returned for modification 29 September 2008/ Accepted 18 October 2008

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.

* Corresponding author. Mailing address: Department of Microbiology, B103 Chemical and Life Science Building, MC 110, 601 South Goodwin Avenue, Urbana, IL 61801. Phone: (217) 244-7940. Fax: (217) 244-6697. E-mail: tapping{at}life.uiuc.edu

{triangledown} Published ahead of print on 27 October 2008.

Editor: J. B. Bliska

Infection and Immunity, January 2009, p. 367-373, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01057-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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