Faculty Collaboration Database

Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions. Genes Immun 2013 Sep;14(6):380-6

Date

05/31/2013

Pubmed ID

23719031

Pubmed Central ID

PMC3766462

DOI

10.1038/gene.2013.32

Scopus ID

2-s2.0-84883850847 (requires institutional sign-in at Scopus site)   4 Citations

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.

Author List

Tsaih SW, Khaja S, Ciecko AE, MacKinney E, Chen YG

Authors

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chromosomes, Mammalian
Diabetes Mellitus, Type 1
Genetic Linkage
Genetic Loci
Genetic Predisposition to Disease
Male
Mice
Mice, Inbred ICR
Mice, Inbred NOD
Natural Killer T-Cells
Quantitative Trait Loci
Spleen
T-Lymphocyte Subsets
Thymus Gland