Rig-I-/- mice develop colitis associated with downregulation of G alpha i2

Cell Res. 2007 Oct;17(10):858-68. doi: 10.1038/cr.2007.81.


RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I(-/-) mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I(-/-) mice are viable and fertile. Histological analysis shows that Rig-I(-/-) mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein alpha i2 subunit (G alpha i2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated G alpha i2 expression. Moreover, G alpha i2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of G alpha i2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of G alpha i2 and disturbed T-cell homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Colitis / chemically induced
  • Colitis / genetics*
  • Colitis / pathology
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology
  • Dextran Sulfate / toxicity
  • GTP-Binding Protein alpha Subunit, Gi2 / genetics*
  • GTP-Binding Protein alpha Subunit, Gi2 / metabolism
  • GTP-Binding Protein alpha Subunit, Gi2 / physiology
  • Mice
  • Mice, Knockout
  • NIH 3T3 Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism


  • Dextran Sulfate
  • Ddx58 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • GTP-Binding Protein alpha Subunit, Gi2