(SWR x SJL)F1 mice: a new model of lupus-like disease.
During the study of autoimmune models we found that (SWR x SJL)F1 mice (both parental strains with the V beta a phenotype) spontaneously produced immunoglobulin G (IgG) antibodies directed against Sm/U1 small nuclear ribonucleoproteins (snRNPs). In some of these females, the presence of these autoantibodies was found as early as 10 wk of age. Their frequency increased with age i.e., 70% at 40 wk. At that time, only 10% of males developed anti-Sm/U1snRNP antibodies. Anti-Sm/U1snRNP antibodies from positive mice generally recognized the peptides BB', D, 70 kD, and A from RNPs. These polypeptides are known to bear the autoantigenic epitopes that are recognized by human sera containing anti-Sm and anti-U1snRNP antibodies. Reactivity of IgG antibodies with the octapeptide sequence PPPGMRPP was also found in 30% of anti-Sm/U1snRNP positive (SWR x SJL)F1 mice that precipitated BB' peptides. This octapeptide has been described as the most immunoreactive linear epitope in systemic lupus erythematosus (SLE) patients with anti-Sm and anti-U1snRNP antibodies. Approximately 30% of anti-Sn/U1snRNP positive females, later produced anti-dsDNA antibodies. This fact was accompanied by the development of proteinuria due to glomerulonephritis mediated by immunocomplexes. In addition to the specific autoimmune response, (SWR x SJL)F1 females also showed other immunologic abnormalities such as hypergammaglobulinemia, and an approximately twofold increase in spleen cell number compared with control mice. These results indicate that (SWR x SJL)F1 females develop clinical and serological abnormalities similar to those observed in human SLE and constitute a novel model for the study of the genetic mechanisms that result in autoimmunity.
Vidal
S
S
Department of Immunology, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Spain.
Gelpí
C
C
Rodríguez-Sánchez
J L
JL
D000818:Animals; D000941:Antigens / Q000276:immunology; D015415:Biomarkers; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008177:Lupus Vulgaris / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012342:RNA, Small Nuclear / Q000276:immunology
D000941:Antigens; D015415:Biomarkers; D007074:Immunoglobulin G; D012342:RNA, Small Nuclear