Subcongenic analysis of genetic basis for impaired development of invariant NKT cells in NOD mice.
Document Type
Article
Publication Date
2007
Keywords
Antigens-CD1, Diabetes-Mellitus-Type-1, Genetic-Predisposition-to-Disease, Killer-Cells-Natural, Lymphocyte-Activation, Lymphocyte-Count, Mice-Congenic, Mice-Inbred-NOD, Species-Specificity
First Page
705
Last Page
712
JAX Source
Immunogenetics 2007 Sep; 59(9):705-12.
Abstract
Reduced numbers and function of invariant NKT (iNKT) cells partially contribute to type 1 diabetes (T1D) development in NOD mice. Previous linkage analysis identified a genetic locus on chromosome 2 controlling numbers of thymic iNKT cells. Interestingly, this locus resides within the Idd13 region that distinguishes NOD mice from the closely genetically related, but strongly T1D-resistant NOR strain. Thus, we tested if a genetic variant that confers T1D resistance in NOR mice may do so by enhancing iNKT cell numbers. iNKT cells were enumerated by an alpha-GalCer analog loaded CD1d tetramer in NOD and NOR mice as well as in NOD stocks carrying NOR-derived congenic regions on chromosome 1, 2, or 4. Significantly, more thymic and splenic iNKT cells were present in NOR than NOD mice. The NOR-derived Idd13 region on chromosome 2 contributed the most significant effect on increasing iNKT cell numbers. Subcongenic analyses indicated that at least two genes within the Idd13 region regulate iNKT cell numbers. These results further define the genetic basis for numerical iNKT cell defects contributing to T1D development in NOD mice.
Recommended Citation
Chen YG,
Driver JP,
Silveira PA,
Serreze DV.
Subcongenic analysis of genetic basis for impaired development of invariant NKT cells in NOD mice. Immunogenetics 2007 Sep; 59(9):705-12.