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* Comparative Genomics Center, James Cook University, Townsville, Queensland, Australia; and
University of Melbourne, Department of Microbiology and Immunology, Parkville, Victoria, Australia
Invariant NKT cells play a critical role in controlling the strength and character of adaptive immune responses. We have previously reported deficiencies in the numbers and function of NKT cells in the NOD mouse strain, which is a well-validated model of type 1 diabetes and systemic lupus erythematosus. Genetic control of thymic NKT cell numbers was mapped to two linkage regions: Nkt1 on distal chromosome 1 and Nkt2 on chromosome 2. In this study, we report the production and characterization of a NOD.Nkrp1b.Nkt1b congenic mouse strain, apply microarray expression analyses to limit candidate genes within the 95% confidence region, identify Slamf1 (encoding signaling lymphocyte activation molecule) and Slamf6 (encoding Ly108) as potential candidates, and demonstrate retarded signaling lymphocyte activation molecule expression during T cell development of NOD mice, resulting in reduced expression at the CD4+CD8+ stage, which is consistent with decreased NKT cell production and deranged tolerance induction in NOD mice.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 A.G.B. is supported by an Australian National Health and Medical Research Council Senior Research Fellowship, J.M.F. is the recipient of an Australian Postgraduate Award, and M.A.J. is the recipient of a James Cook University intramural scholarship. This project was funded by the Australian National Health and Medical Research Council.
2 M.A.J. and J.M.F. contributed equally to this manuscript.
3 Address correspondence and reprint requests to Dr. Alan G. Baxter, Comparative Genomics Center, Molecular Sciences Building 21, James Cook University, Townsville, Queensland 4811, Australia. E-mail address: Alan.Baxter{at}jcu.edu.au
4 Abbreviations used in this paper: iNKT, invariant NKT; CD1d/
-GalCer, CD1/
-galactosylceramide; DP, double positive; SAP, SLAM-associated protein; SH, Src homology; SLAM, signaling lymphocyte activation molecule; SP, single positive.
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