Polymorphisms in the II12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains
- Author(s)
- Ymer, SI; Huang, D; Penna, G; Gregori, S; Branson, K; Adorini, L; Morahan, G;
- Details
- Publication Year 2002-05,Volume 3,Issue #3,Page 151-157
- Journal Title
- GENES AND IMMUNITY
- Publication Type
- Journal Article
- Abstract
- Interleukin (II)-12 is a heterodimeric cytokine composed of 35 and 40 kD chains that plays a key role in the induction of Th1 cells, a T cell subset involved in many autoimmune diseases. We report here the cDNA sequence encoding the IL-12 p40 subunit from the autoimmune-prone non-obese diabetic (NOD) mouse, which spontaneously develops type 1 diabetes. Compared with the C57BL/6 sequence, there are two base changes that lead to amino acid replacements. Other autoimmune-prone strains, but not the diabetes-resistant NOR strain, share the same allele as NOD. We found both trans- and cis- allele-dependent effects on levels of basal and induced IL-12p40 expression. Furthermore, we show that one of these changes results in a structural change in the p40 molecule, as evidenced by the failure of a monoclonal antibody to bind NOD IL-12. These findings have implications for the predisposition to autoimmune responses in NOD and other autoimmune-prone mouse strains.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- NONOBESE DIABETIC MICE; P40 SUBUNIT; INTERLEUKIN (IL)-12; SUSCEPTIBILITY; MACROPHAGES; ANTAGONIST; INTERFERON; INDUCTION; RECEPTOR; MELLITUS
- Publisher's Version
- https://doi.org/10.1038/sj/gene/6363849
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-05-01 12:00:00