TY - JOUR
T1 - An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus
AU - Zhang, M. C.
AU - Misu, N.
AU - Furukawa, H.
AU - Watanabe, Y.
AU - Terada, M.
AU - Komori, H.
AU - Miyazaki, T.
AU - Nose, M.
AU - Ono, Masao
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
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U2 - 10.1136/ard.2005.040832
DO - 10.1136/ard.2005.040832
M3 - Article
C2 - 16150787
AN - SCOPUS:33645120316
SN - 0003-4967
VL - 65
SP - 495
EP - 500
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 4
ER -