Cuttine edge: diabetes-associated quantitative trait locus, Idd4, is responsible for the IL-12p40 overexpression defect in nonobese diabetic (NOD) mice.
APCs of the nonobese diabetic (NOD) mouse have a genetically programmed capacity to overexpress IL-12p40, a cytokine critical for development of pathogenic autoreactive Th1 cells. To determine whether a diabetes-associated NOD chromosomal locus (i.e., Idd) was responsible for this defect, LPS-stimulated macrophages from several recombinant congenic inbred mice with Idd loci on a C57BL/6 background or with different combinations of NOD and CBA genomic segments were screened for IL-12p40 production. Only macrophages from the congenic strains containing the Idd4 locus showed IL-12p40 overproduction/expression. Moreover, analysis of IL-12p40 sequence polymorphisms demonstrated that the Idd4 intervals in these strains contained the IL-12p40 allele of the NOD, although further analysis is required to determine whether the IL-12p40 allele itself is responsible for its overexpression. Thus, the non-MHC-associated Idd4 locus appears responsible for IL-12p40 overexpression, which may be a predisposing factor for type 1 diabetes in NOD mice.
D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D016678:Genome; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D053762:Interleukin-12 Subunit p40; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD / Q000235:genetics* / Q000276:immunology*; D021122:Protein Subunits / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D040641:Quantitative Trait Loci / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis
D005819:Genetic Markers; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12