Mouse models for Aicardi-Goutières syndrome provide clues to the molecular pathogenesis of systemic autoimmunity

Clin Exp Immunol. 2014 Jan;175(1):9-16. doi: 10.1111/cei.12147.


Aicardi-Goutières syndrome (AGS) is a hereditary autoimmune disease which overlaps clinically and pathogenetically with systemic lupus erythematosus (SLE), and can be regarded as a monogenic variant of SLE. Both conditions are characterized by chronic activation of anti-viral type I interferon (IFN) responses. AGS can be caused by mutations in one of several genes encoding intracellular enzymes all involved in nucleic acid metabolism. Mouse models of AGS-associated defects yielded distinct phenotypes and reproduced important features of the disease. Analysis of these mutant mouse lines stimulated a new concept of autoimmunity caused by intracellular accumulations of nucleic acids, which trigger a chronic cell-intrinsic antiviral type I IFN response and thereby autoimmunity. This model is of major relevance for our understanding of SLE pathogenesis. Findings in gene-targeted mice deficient for AGS associated enzymes are summarized in this review.

Keywords: Aicardi-Goutières syndrome; SLE; interferon; nucleic acid sensing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases of the Nervous System* / genetics
  • Autoimmune Diseases of the Nervous System* / immunology
  • Autoimmune Diseases of the Nervous System* / pathology
  • Autoimmunity / genetics*
  • Disease Models, Animal
  • Gene Targeting
  • Humans
  • Interferon Type I* / genetics
  • Interferon Type I* / immunology
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Erythematosus, Systemic* / immunology
  • Lupus Erythematosus, Systemic* / pathology
  • Mice
  • Mice, Mutant Strains
  • Nervous System Malformations* / genetics
  • Nervous System Malformations* / immunology
  • Nervous System Malformations* / pathology


  • Interferon Type I

Supplementary concepts

  • Aicardi-Goutieres syndrome