Genetic control of NKT cell numbers maps to major diabetes and lupus loci.
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.Nkrp1(b) 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.
Esteban
Luis M
LM
Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
Tsoutsman
Tatiana
T
Jordan
Margaret A
MA
Roach
Daniel
D
Poulton
Lynn D
LD
Brooks
Andrew
A
Naidenko
Olga V
OV
Sidobre
Stephane
S
Godfrey
Dale I
DI
Baxter
Alan G
AG
D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D002874:Chromosome Mapping / Q000379:methods; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D008040:Genetic Linkage / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D005819:Genetic Markers