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Genetics of SLE: evidence from mouse models

Nature Reviews Rheumatology volume 6, pages 348–357 (2010)Cite this article

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Abstract

Great progress has been made in the field of lupus genetics in the past few years, notably with the publication of genome-wide association studies in humans and the identification of susceptibility genes (including Fcgr2b, Ly108, Kallikrein genes and Coronin-1A) in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. Studies in the 1980s and 1990s established that mice prone to spontaneous lupus constitute excellent models of the genetic architecture of human systemic lupus erythematosus (SLE). This notion has been greatly strengthened by the convergence of the functional pathways that are defective in both human and murine lupus. Within these pathways, variants in a number of genes have now been shown to be directly associated with lupus in both species. Consequently, mouse models will continue to serve a pre-eminent role in lupus genetics research, with an increased emphasis on mechanistic and molecular studies of human susceptibility alleles.

Key Points

  • A large number of lupus susceptibility loci have been validated in mouse models, and the corresponding susceptibility genes have been identified for some of these loci

  • Many murine lupus genes characterized by congenic studies have been validated in association studies in patients with systemic lupus erythematosus (SLE)

  • In both mice and humans, lupus susceptibility results from the combination of the weak individual effects of a large number of alleles

  • The functional pathways that are defective in both human and murine lupus largely overlap

  • The functional characterization of SLE risk alleles identified by analyses of genome-wide association studies will greatly benefit from mechanistic and molecular studies in mouse models

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  1. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, 1600 Archer Road, Gainesville, 32610-0275, FL, USA

    Laurence Morel

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Supplementary information

Supplementary Box 1

The mouse geneticist's tool box (DOC 44 kb)

Supplementary Table 1

Genes associated with lupus in murine transgenic models and validated in patients with SLE (DOC 83 kb)

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Morel, L. Genetics of SLE: evidence from mouse models. Nat Rev Rheumatol 6, 348–357 (2010). https://doi.org/10.1038/nrrheum.2010.63

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