title: Mouse models for Aicardi-Goutières syndrome provide clues to the molecular pathogenesis of systemic autoimmunity.
abstract: 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.
authors.affiliation: Institute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Dresden, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Behrendt
authors.forename: A
authors.initials: A
authors.lastname: Roers
mesh_terms: D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics*; D004195:Disease Models, Animal; D018390:Gene Targeting; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009421:Nervous System Malformations / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D007370:Interferon Type I
keywords: Aicardi-Goutières syndrome; SLE; interferon; nucleic acid sensing