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

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

Author information

1
Institute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Dresden, Germany.

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.

KEYWORDS:

Aicardi-Goutières syndrome; SLE; interferon; nucleic acid sensing

PMID:
23713592
PMCID:
PMC3898549
DOI:
10.1111/cei.12147
[Indexed for MEDLINE]
Free PMC Article

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