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Paper Chase

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

Proc. Natl. Acad. Sci. U.S.A.. May 18, 2010;107(20):9305-10.
Suwanai H, Wilcox MA, Mathis D, Benoist C.

Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA.


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.