Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains

Genes Immun. 2002 May;3(3):151-7. doi: 10.1038/sj.gene.6363849.

Abstract

Interleukin (Il)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • DNA, Complementary
  • Gene Expression Regulation*
  • Interleukin-12 / genetics*
  • Interleukin-12 / immunology
  • Interleukin-12 Subunit p40
  • Mice
  • Mice, Inbred NOD
  • Mice, Inbred Strains / genetics
  • Mice, Inbred Strains / metabolism
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Protein Subunits / genetics*
  • Protein Subunits / immunology
  • Sequence Alignment

Substances

  • Antibodies, Monoclonal
  • DNA, Complementary
  • Interleukin-12 Subunit p40
  • Protein Subunits
  • Interleukin-12