Autoimmune diseases get the NOD

Type 1 diabetes (also known as insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease in which the patient's immune system destroys insulin-producing β cells of the pancreatic islets of Langerhans. The NOD (non-obese diabetic) mouse has served as a powerful animal model for deciphering the complex genetic contributions to IDDM disease. In the February Nature Genetics, Morahan et al. describe the identification of IDDM18, a new locus associated with human type 1 diabetes, following a hint from studies of NOD mice (Nat Genet 2001, 27:218-221). A search for human homologs of NOD diabetes susceptibility loci led Morahan and colleagues to the human IL12B gene, which encodes a subunit of the interleukin 12 (IL-12) cytokine. They type 249 sibpairs for markers at the IL12B locus on chromosome 5q33-34. HLA-identical pairs showed strong linkage to this region. They identified a polymorphism in the 3' UTR of IL12Bthat appears to confer susceptibility by altering the levels of IL-12 expression. It is possible that the effect IL-12 has on regulating T-cell responses plays a role in other autoimmune diseases.