First Author | Vidal S | Year | 1994 |
Journal | J Exp Med | Volume | 179 |
Issue | 5 | Pages | 1429-35 |
PubMed ID | 8163929 | Mgi Jnum | J:17879 |
Mgi Id | MGI:65903 | Doi | 10.1084/jem.179.5.1429 |
Citation | Vidal S, et al. (1994) (SWR x SJL)F1 mice: a new model of lupus-like disease. J Exp Med 179(5):1429-35 |
abstractText | 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. |