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  • Original Article
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Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis

Genes & Immunity volume 8, pages 634–645 (2007)Cite this article

Abstract

Genetic analyses of the lupus-prone NZM2410 mouse have identified multiple susceptibility loci on chromosome 7, termed Sle3 and Sle5. Both of these loci were contained within a large congenic interval, originally termed as Sle3 that strongly impacts a variety of myeloid and T-cell phenotypes and mediates fatal lupus nephritis when combined with Sle1. We have now produced two subcongenic strains, B6.Sle3 and B6.Sle5, carrying the Sle3 and Sle5 intervals separately and characterized their phenotypes as monocongenic strains and individually in combination with Sle1. Neither B6.Sle3 nor B6.Sle5 monocongenic strain develop severe autoimmunity; however, both of these intervals cause the development of severe glomerulonephritis when combined with Sle1. Thus, B6.Sle1Sle3 and B6.Sle1Sle5 exhibit splenomegaly, expansion of activated B and CD4+ T-cell populations and high levels of IgG and IgM autoantibodies targeting multiple nuclear antigens, intact glomeruli and various other autoantigens. In addition, B6.Sle1Sle3 mice also produced higher levels of IgA antinuclear autoantibodies, which were implicated in the development of IgA nephropathy. Our results indicate that Sle3 and Sle5 can independently complement with Sle1, through shared and unique mechanisms, to mediate the development of severe autoimmunity.

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Acknowledgements

We thank Dr Nicolai van Oers for critical reading of this manuscript. We also thank Dr Jose Casco for the management of the mouse colony. This work was supported by grants from the National Institutes of Health (PO1 AI 39824 to EK Wakeland) and Alliance for Lupus Research (EK Wakeland). K Liu was a recipient of National Institutes of Health National Research Service Award (5 F32 AR48058).

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Authors and Affiliations

  1. Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    K Liu, Q Z Li, C Liang, S Subramanian, Z Zeng, C Mohan & E K Wakeland

  2. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA

    Y Yu

  3. Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    H W Wang & X J Zhou

  4. Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    C Xie, X J Zhou & C Mohan

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  1. K Liu
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  2. Q Z Li
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Correspondence to K Liu or E K Wakeland.

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Liu, K., Li, Q., Yu, Y. et al. Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis. Genes Immun 8, 634–645 (2007). https://doi.org/10.1038/sj.gene.6364426

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  • DOI: https://doi.org/10.1038/sj.gene.6364426

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