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An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus
  1. M-C Zhang1,
  2. N Misu1,
  3. H Furukawa1,
  4. Y Watanabe2,
  5. M Terada2,
  6. H Komori2,
  7. T Miyazaki2,
  8. M Nose2,
  9. M Ono1
  1. 1Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
  2. 2Department of Pathology, Ehime University School of Medicine, Toon, Japan
  1. Correspondence to:
    Professor Masao Ono
    Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba-ku, Sendai, Miyagi 980-8575, Japan; onomasao{at}mail.tains.tohoku.ac.jp

Abstract

Objective: To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus.

Methods: Vasculitis of renal arteries was histopathologically evaluated in MRL/Mp-Faslpr (MRL/lpr), C57BL/6-Faslpr (B6/lpr), (MRL/lpr×B6/lpr) F1, and MRL/lpr×(MRL/lpr×B6/lpr) F1 backcross mice. Using genomic DNA samples of the backcross mice, genome-wide scans, association studies, and linkage analyses were carried out based on genotypes of polymorphic microsatellite markers. Correlations of vasculitis grade and levels of various autoantibodies were also evaluated.

Results: Two recessive susceptibility loci of the MRL allele were identified on chromosomes 4 and 1, which had previously been defined as the autoimmune related loci termed Arvm1 and Sle-1/Nba2, respectively. The former was epistatic to the latter in a female specific manner. The titre of antinuclear autoantibody (ANA) in IgG class, but not ANA in IgM class or anti-dsDNA in either IgG or IgM class, correlated significantly with vasculitis grade.

Conclusions: The present loci have been reported in previous studies using a different set of murine strains, suggesting that they are of importance in the development of autoimmune vasculitis in murine models. The concomitance of autoimmune vasculitis and IgG ANA suggests a shared genetic factor regulating these traits.

  • ANA, antinuclear autoantibody
  • QTL, quantitative trait locus
  • SLE, systemic lupus erythematosus
  • vasculitis
  • autoimmunity
  • genetics
  • mouse

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Footnotes

  • Published Online First 8 September 2005

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