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Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus

Genes & Immunity volume 7, pages 592–599 (2006)Cite this article

Abstract

Systemic lupus erythematosus is an autoimmune disease in which complex interactions between genes and environmental factors determine the disease phenotype. We have shown that genes from the non-autoimmune strains 129 and C57BL/6 (B6), commonly used for generating gene-targeted animals, can induce a lupus-like disease. Here, we conducted a genome-wide scan analysis of a cohort of (129 × B6)F2 C1q-deficient mice to identify loci outside the C1qa locus contributing to the autoimmune phenotype described in these mice. The results were then confirmed in a larger dataset obtained by combining the data from the C1q-deficient mice with data from previously reported wild-type mice. Both analyses showed that a 129-derived interval on distal chromosome 1 is strongly linked to autoantibody production. The B6 genome contributed to anti-nuclear autoantibody production with an interval on chromosome 3. Two regions were linked to glomerulonephritis: a 129 interval on proximal chromosome 7 and a B6 interval on chromosome 13. These findings demonstrate that interacting loci between 129 and B6 mice can cause the expression of an autoimmune phenotype in gene-targeted animals in the absence of any disrupted gene. They also indicate that some susceptibility genes can be inherited from the genome of non-autoimmune parental strains.

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Abbreviations

Abs:

antibodies

AEU:

arbitrary ELISA units

ANA:

antinuclear antibody

AP:

alkaline phosphatase

anti-dsDNA:

anti-double stranded DNA

anti-ssDNA:

anti-single stranded DNA

B6:

C57BL/6

GN:

glomerulonephritis

QTL:

quantitative trait locus

SLE:

Systemic lupus erythematosus

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Acknowledgements

We thank Mrs Margarita Lewis for technical assistance with the processing of tissue for histological studies and the staff of the Biological Services Unit at our institution for the care of the animals involved in this study. This work was supported by the Wellcome Trust (Grant number 071467).

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Author notes

  1. M J Walport

    Present address: The Wellcome Trust, London, UK

  2. Y Heidari and A E Bygrave: These authors equally contributed to the work.

Authors and Affiliations

  1. Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK

    Y Heidari, A E Bygrave, R J Rigby, K L Rose, M J Walport, T J Vyse & M Botto

  2. Department of Histopathology, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK

    H T Cook

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  1. Y Heidari
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  2. A E Bygrave
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  7. T J Vyse
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Correspondence to M Botto.

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Heidari, Y., Bygrave, A., Rigby, R. et al. Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus. Genes Immun 7, 592–599 (2006). https://doi.org/10.1038/sj.gene.6364335

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