Genetic control of NKT cell numbers maps to major diabetes and lupus loci

Esteban, Luis M., Tsoutsman, Tatiana, Jordan, Margaret A., Roach, Daniel, Poulton, Lynn D., Brooks, Andrew, Naidenko, Olga V., Sidobre, Stephane, Godfrey, Dale I., and Baxter, Alan G. (2003) Genetic control of NKT cell numbers maps to major diabetes and lupus loci. Journal of Immunology, 171 (6). pp. 2873-2878.

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Natural killer T cells are an immunoregulatory population of lymphocytes that plays a critical role in controlling the adaptive immune system and contributes to the regulation of autoimmune responses. We have previously reported deficiencies in the numbers and function of NKT cells in the nonobese diabetic (NOD) mouse strain, a well-validated model of type 1 diabetes and systemic lupus erythematosus. In this study, we report the results of a genetic linkage analysis of the genes controlling NKT cell numbers in a first backcross (BC1) from C57BL/6 to NOD.Nkrp1b mice. The numbers of thymic NKT cells of 320 BC1 mice were determined by fluorescence-activated cell analysis using anti-TCR Ab and CD1/{alpha}-galactosylceramide tetramer. Tail DNA of 138 female BC1 mice was analyzed for PCR product length polymorphisms at 181 simple sequence repeats, providing greater than 90% coverage of the autosomal genome with an average marker separation of 8 cM. Two loci exhibiting significant linkage to NKT cell numbers were identified; the most significant (Nkt1) was on distal chromosome 1, in the same region as the NOD mouse lupus susceptibility gene Babs2/Bana3. The second most significant locus (Nkt2) mapped to the same region as Idd13, a NOD-derived diabetes susceptibility gene on chromosome 2.

Item ID: 6607
Item Type: Article (Research - C1)
ISSN: 1550-6606
Keywords: diabetes; immunology; lupus; NKT cells
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Date Deposited: 11 Feb 2010 00:51
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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