An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus.
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.
Zhang
M-C
MC
Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Misu
N
N
Furukawa
H
H
Watanabe
Y
Y
Terada
M
M
Komori
H
H
Miyazaki
T
T
Nose
M
M
Ono
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002874:Chromosome Mapping / Q000379:methods; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018895:Microsatellite Repeats; D012077:Renal Artery / Q000473:pathology; D012720:Severity of Illness Index; D014657:Vasculitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D000974:Antibodies, Antinuclear