| First Author | Ito MR | Year | 1997 |
| Journal | Arthritis Rheum | Volume | 40 |
| Issue | 6 | Pages | 1054-63 |
| PubMed ID | 9182916 | Mgi Jnum | J:41268 |
| Mgi Id | MGI:893438 | Doi | 10.1002/art.1780400610 |
| Citation | Ito MR, et al. (1997) Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand. Arthritis Rheum 40(6):1054-63 |
| abstractText | Objective. To characterize Fas antigen expression on the cell surface, and to determine the effect of this expression in rheumatic diseases using a newly established gld-congenic MRL strain of mice (MRL/gld), which is defective in its functional Fas ligand (Fas-L). Methods. Flow cytometric analyses of lymphoid cells and macrophages were performed using anti-Fas and other cell surface markers, Histopathologic manifestations were examined using immunochemistry and light and electron microscopy, Serum levels of IgG and anti-DNA antibodies were measured by single radial immunodiffusion and enzyme- linked immunosorbent assay, respectively. Results. MRL/gld mice developed systemic lymphadenopathy with an accumulation of Thy1.2+, B220+ and CD4-, CD8- T cells, which both express the Fas antigen, Splenic B cells positive for surface IgM and/or surface IgD, and resident peritoneal macrophages exhibited lip-regulated expression of the Fas antigen, at much higher levels than those observed in MRL/MpJ.+/+ (MRL/+) mice, Forms of rheumatic disease were observed in these mice, although not in C3H/HeJ-gld/gld mice, These forms included diffuse glomerulonephritis, granulomatous arteritis, and arthritis, and were associated with the infiltration of mononuclear cells expressing the Fas antigen, Serum levels of IgG and anti-DNA antibodies were significantly increased in MRL/gld mice compared with MRL/+ mice. Conclusion. Rheumatic disease was generated by the gin gene in mice with an MRL background, as it is by the lpr gene, which is a Fas deletion mutant, associated with autoimmune traits, Rheumatic disease in this MRL strain was initiated by an incapacity for Fas/Fas-L-induced apoptosis, resulting in the development of autoimmunity and allowing for a persistent immune response in the affected lesions. |
