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Genetic Approach to Study Lupus Glomerulonephritis

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Autoimmunity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 900))

Abstract

Genetic and environmental factors contribute in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis, the most common and severe manifestation of SLE, involves inflammation in the kidney leading to loss of renal function. However, it is not clear what controls the progression of lupus nephritis; this is an important research question, considering its implications in clinical treatment of lupus nephritis. Finding genes that underlie the development and progression of lupus nephritis will shed light on this question. NZM2328 is a spontaneous mouse model for SLE. Most NZM2328 female mice develop autoantibodies (e.g., antinuclear antibody and anti-dsDNA antibody), glomerulonephritis (GN), and severe proteinuria between 5 and 12 months of age. In contrast, C57L/J mice fail to exhibit similar signs of autoimmune disease. We used classical genetics to map and identify SLE genes in offspring generated by backcrossing C57L/J to NZM2328. Quantitative trait loci (QTL) controlling acute (Agnz1 and Agnz2) and chronic (Cgnz1) GN features were uncovered by the analysis. To verify the Cgnz1 and Agnz1 on distal mouse chromosome 1, we produced the NZM23238.C57Lc1 (Lc1) congenic strain, which replaced NZM2328 Cgnz1 and Agnz1 alleles with those derived from C57L/J. The development of acute GN and chronic GN was markedly reduced in Lc1 mice, confirming the linkage findings. Further mapping by the generation of intrachromosomal recombinants of NZM2328.Lc1 support the thesis that acute GN and chronic GN are under separate genetic control.

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Acknowledgments

This work was supported in part by NIH grants AI050072 (M.G.B.), P50-AR04522, R01-AR047988, R01-AR049449 and R01-AI079621 (S.M.F.) and a grant from Alliance for Lupus Research (S.M.F.).

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Authors and Affiliations

  1. Department of Medicine and Microbiology and Center of Immunity, Inflammation and Regenerative Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA

    Yan Ge, Michael G. Brown, Hongyang Wang & Shu Man Fu

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  1. Yan Ge
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  2. Michael G. Brown
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  3. Hongyang Wang
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  4. Shu Man Fu
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Corresponding author

Correspondence to Shu Man Fu .

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Editors and Affiliations

  1. College of Medicine, Division of Rheumatology, State University of New York, UMU, East Adams St. 750, Syracuse, 13210, New York, USA

    Andras Perl

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Ge, Y., Brown, M.G., Wang, H., Fu, S.M. (2012). Genetic Approach to Study Lupus Glomerulonephritis. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Biology, vol 900. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-720-4_13

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  • DOI: https://doi.org/10.1007/978-1-60761-720-4_13

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-719-8

  • Online ISBN: 978-1-60761-720-4

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