Polymorphisms in the II12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains

S.I. Ymer, D. Huang, G. Penna, S. Gregori, K. Branson, L. Adorini, Grant Morahan

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)151-157
JournalGenes and Immunity
Volume3
DOIs
Publication statusPublished - 2002

Fingerprint

Dive into the research topics of 'Polymorphisms in the II12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains'. Together they form a unique fingerprint.

Cite this