title: Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions.
abstract: Reduced frequency of invariant natural killer T (iNKT) cells has been indicated as a contributing factor to type 1 diabetes (T1D) development in NOD mice. To further understand the genetic basis of the defect, we generated (NOD × ICR)F2 mice to map genes that control iNKT-cell development. We determined frequencies of thymic and splenic iNKT cells, as well as the ratio of CD4-positive and -negative subsets in the spleens of 209 F2 males. Quantitative trait loci (QTL) analysis revealed five loci that exceed the significant threshold for the frequency of thymic and/or splenic iNKT cells on Chromosomes (Chr) 1, 5, 6, 12 and 17. Three significant loci on Chr 1, 4 and 5 were found for the ratio of CD4-positive and -negative splenic iNKT cells. Comparisons with previously known mouse T1D susceptibility (Idd) loci revealed two significant QTL peak locations, respectively, mapped to Idd regions on Chr 4 and 6. The peak marker location of the significant Chr 12 iNKT QTL maps to within 0.5 Mb of a syntenic human T1D locus. Collectively, our results reveal several novel loci controlling iNKT-cell development and provide additional information for future T1D genetic studies.
authors.affiliation: Medical College of Wisconsin, Human and Molecular Genetics Center, Milwaukee, WI 53226, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Tsaih
authors.forename: S
authors.initials: S
authors.lastname: Khaja
authors.forename: A E
authors.initials: AE
authors.lastname: Ciecko
authors.forename: E
authors.initials: E
authors.lastname: MacKinney
authors.forename: Y G
authors.initials: YG
authors.lastname: Chen
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D008040:Genetic Linkage; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D055611:Natural Killer T-Cells / Q000166:cytology*; D040641:Quantitative Trait Loci; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology