Experiment
Inbred strain NOD displays reduced iNKT cell number and function compared to inbred strain C57BL/6. NOD mice have 1/3 to 1/2 the number of iNKT cells in thymus, liver, and spleen compared to C57BL/6. In addition, iNKT cells of NOD mice exhibit deficientcytokine response when induced with antigen. The association of previously identified insulin dependent diabetes (Idd) loci with the iNKT phenotype was analyzed in congenic animals derived from NOD and C57BL/6.
Congenic line NOD.B10-Idd9 (R28) carries aC57BL/10-derived region of mouse Chromosome 4 encompassing Idd9 (82 cM) on an NOD genetic background. This congenic exhibits partial restoration of iNKT cell numbers but the defective cytokine response resembles that of NOD.
Comparison of sub-congenic lines carrying C57BL/10-derived regions of Idd9.2 (strain R35) and Idd9.2 + Idd9.3 (R11) were compared to the full Idd9 congenic (R28). Strains R35 and R11 display iNKT cell numbers similar to the NOD strain whereas strain R28 displays increased iNKT cell numbers. Therefore authors conclude that regulation of iNKT cell maintenance is associated with Idd9.1. This locus is also associated with the IFN-gamma response in natural killer (NK) cells when challenged with antigen. Candidate genes mapping to the Idd9.1 region include Il14 (**note: Il14 is not found in MGI or the Human Gene Nomenclature Database**) and Lck.
The B6.NOD-Idd6 congenic carries an NOD-derived region of mouse Chromosome 6 encompassing the Idd6 locus (73 cM) on a C57BL/6 genetic background. This congenic displays defective IFN-gamma response when challenged with antigens. Therefore authors conclude that the Idd6 locus plays a role in the cytokine response of NK cells.
The B6.NOD-Idd3,Idd10 congenic carries an NOD-derived region of mouse Chromosome 3 encompassing Idd3 (19.2 cM) and Idd10 (48.5 cM) on a C57BL/6 genetic background. This strain displays normal numbers of NKT cells but have a defective cytokine response (IL-2, IL-4, IFN-gamma, CSF-2) when challenged with antigen. Therefore, authors associate the Idd3 and Idd10 loci on chromosome 3 with NKT cell cytokine response.
The B6.NOD-Idd13 congenic carries an NOD-derived region of mouse Chromosome 2 encompassing Idd13 (71 cM) on a C57BL/6 genetic background. This strain displays normal numbers of NKT cells but have a defective cytokine response (IL-2, IL-4, IFN-gamma, CSF-2) when challenged with antigen. Therefore, authors associate the Idd13 locus on chromosome 2 with NKT cell cytokine response.
The B6.NOD-Idd4 congenic carries anNOD-derived region of mouse Chromosome 11 encompassing Idd4 (46 cM) on a C57BL/6 genetic background. This congenic displays reduced iNKT cell numbers in the liver (but normal numbers of iNKT in the spleen and thymus) and reduced NKT cytokine response when challenged with antigen. Authors concluded the Idd4 locus is associated with maintenance and/or hepatic homing of iNKT cell number. Csf2 is a candidate gene mapping to the Idd4 region. When Csf2 knockout mice were crossed to the B6.NOD-Idd4 congenic, rescue of the low iNKT cell number and defective cytokine response phenotypes was rescued, indicating that Csf2 is not the gene underlying Idd4.
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