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

Proc Natl Acad Sci U S A. 2010 May 18;107(20):9305-10. doi: 10.1073/pnas.1004492107. Epub 2010 May 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Chromosome Mapping
  • Crosses, Genetic
  • Genotype
  • Interleukin-15 / genetics*
  • Interleukin-15 / immunology*
  • Killer Cells, Natural / immunology*
  • Lod Score
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Microarray Analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Interleukin-15