Arteritis in a novel congenic strain of mice derived from MRL/Lpr lupus mice: genetic dissociation from glomerulonephritis and limited autoantibody production.
An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis and glomerulone phritis in the same individual, and both have been thought to be associated with an increase in circulating immune complexes and autoantibodies. However, the genetic basis of these diseases is poorly understood. A novel recombinant congenic mouse strain, McH5-lpr/lpr, which was established by rearrangement of the genetic background of MRL/lpr mice by hybridization with C3H/HeJ-lpr/lpr mice, developed severe granulomatous polyarteritis, as did the MRL/lpr strain, but not glomerulonephritis. Serum levels of anti-DNA and anti-myeloperoxidase antibodies in these mice were significantly reduced, as compared with MRL/lpr mice, although rheumatoid factors were not. These results indicate that each of these two diseases, arteritis and glomerulonephritis, is under the control of different background gene(s), suggesting a different pathological basis of these diseases, and that anti-DNA and anti-myeloperoxidase autoantibodies appear to have a limited pathogenic role in granulomatous arteritis in the mouse strain described.
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
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M
Nose
M
M
Nishimura
M R
MR
Ito
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J
Toh
T
T
Shibata
T
T
Sugisaki
D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood; D001167:Arteritis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000633:toxicity*; D004198:Disease Susceptibility; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes