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

ABSTRACT: 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.

SUBMITTER: Suwanai H

PROVIDER: S-EPMC2889097 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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

Suwanai Hirotsugu H Wilcox Martha Angela MA Mathis Diane D Benoist Christophe C

Proceedings of the National Academy of Sciences of the United States of America 20100503 20

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 bioava ...[more]

PMID: 20439722

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