Slamf1, the NKT cell control gene Nkt1.
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.Nkrp1(b).Nkt1(b) 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.
Jordan
Margaret A
MA
Comparative Genomics Center, James Cook University, Townsville, Queensland, Australia.
Fletcher
Julie M
JM
Pellicci
Daniel
D
Baxter
Alan G
AG
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000166:cytology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D027362:Organic Anion Transport Protein 1 / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes
D015703:Antigens, CD; D027362:Organic Anion Transport Protein 1; D011956:Receptors, Cell Surface; D000071176:Signaling Lymphocytic Activation Molecule Family; C000604062:Slamf1 protein, mouse; C000604063:Slamf6 protein, mouse; C105033:Slc22a6 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1