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-Fas(lpr) (MRL/lpr), C57BL/6-Fas(lpr) (B6/lpr), (MRL/lpr x B6/lpr) F1, and MRL/lpr x (MRL/lpr x 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.