title: 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.
authors.affiliation: Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Suwanai
authors.forename: Martha Angela
authors.initials: MA
authors.lastname: Wilcox
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005838:Genotype; D019409:Interleukin-15 / Q000235:genetics* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008126:Lod Score; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019409:Interleukin-15