A defective Il15 allele underlies the deficiency in natural killer cell activity in nonobese diabetic mice

作者：Suwanai Hirotsugu; Wilcox Martha Angela; Mathis Diane; Benoist Christophe^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(20): 9305-9310.

DOI：10.1073/pnas.1004492107

• type 1 diabetes
• gene mapping
• cytotoxicity
• genetic variation

The nonobese diabetic (NOD) mouse strain has a genetic deficiency in natural killer (NK) cells. This defect underlies this strain's utility in several experimental settings; in particular, it promotes engraftment of human tissue in NOD hosts during the generation of "humanized" mouse models. We have mapped the major NK-cell defect in the NOD vs. C57BL/6 (B6) strain to an inadequately expressed Il15 allele. Treatment of NOD mice with a reagent that specifically enhances interleukin (IL)-15 bioavailability normalized NK-cell numbers and activity in the absence of nonspecific stimulation. These findings raise the possibility of exploiting reagents that impact the IL-15 receptor pathway to facilitate construction of humanized mouse models on non-NOD genetic backgrounds.

• 出版日期2010-5-18