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Scientific article
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The Sgp3 locus on mouse chromosome 13 regulates nephritogenic gp70 autoantigen expression and predisposes to autoimmunity

Published inThe Journal of immunology, vol. 171, no. 7, p. 3872-3877
Publication date2003
Abstract

By interval mapping of a backcross progeny between New Zealand White (NZW) and C57BL/6 (B6) mice bearing the Y chromosome-linked autoimmune acceleration gene Yaa, we previously identified a genetic locus on mid-chromosome 13, here designated as Sgp3, showing a major effect on the expression of a nephritogenic autoantigen, gp70. In this study, the NZW-derived Sgp3 region was transferred by backcross procedure and marker-assisted selection on the B6 background to produce three independent congenic strains B6.NZW-Sgp3/1, -Sgp3/2, and -Sgp3/3. We show that NZW homozygosity at a single 3 centiMorgans ( approximately 12 megabases (Mb)) interval between markers D13Mit142 and D13Mit254 mediates increased basal serum levels of gp70 in B6.NZW-Sgp3/1 and B6.NZW-Sgp3/2 mice and with a higher degree in males ( approximately 15 micro g/ml) than in females ( approximately 9 micro g/ml) as compared with B6 ( approximately 2 micro g/ml), revealing a gender effect. However, their gp70 levels are still lower than that of NZW mice ( approximately 60 micro g/ml). In addition, B6.NZW-Sgp3/1 and B6.NZW-Sgp3/2 mice showed a moderate 2- to 3-fold increase in serum gp70 in response to LPS, which contrasted with over a 10-fold increase in NZW mice. Although both B6.NZW-Sgp3/1 and B6.NZW-Sgp3/2 mice failed to produce significant amounts of gp70 anti-gp70 immune complexes, unexpectedly, aged B6.NZW-Sgp3/2 congenic males bearing the Yaa gene developed increased titers of IgG autoantibodies to DNA and chromatin. Our data indicate that Sgp3 is involved in a complex process of gp70 production under polygenic control and may provide a significant contribution to lupus susceptibility not only through up-regulation of gp70 autoantigen production but also predisposition to autoimmunity.

Keywords
  • Animals
  • Antibodies, Antinuclear/biosynthesis/blood
  • Autoantigens/ biosynthesis/blood/genetics
  • Chromatin/immunology
  • Chromosome Mapping/methods
  • Clusterin
  • Crosses, Genetic
  • Female
  • Genetic Markers/ immunology
  • Genetic Predisposition to Disease
  • Glycoproteins/ biosynthesis/blood/ genetics/physiology
  • Immunoglobulin G/biosynthesis/blood
  • Lipopolysaccharides/administration & dosage
  • Lupus Nephritis/ genetics/immunology
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Molecular Chaperones/blood/ genetics/physiology
  • Mutation
  • Species Specificity
  • Y Chromosome/genetics
Affiliation Not a UNIGE publication
Citation (ISO format)
LAPORTE, Catherine et al. The Sgp3 locus on mouse chromosome 13 regulates nephritogenic gp70 autoantigen expression and predisposes to autoimmunity. In: The Journal of immunology, 2003, vol. 171, n° 7, p. 3872–3877. doi: 10.4049/jimmunol.171.7.3872
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ISSN of the journal0022-1767
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