The SCID mouse - A novel experimental model for gene therapy in human rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by a progressive destruction of joints accompanied by synovial hyperplasia, inflammation and autoimmune phe nomena. RA is a common disease, but current animal models resemble human RA only to a limited extent. As recent experimental approaches support the co ncept that T-cell-independent pathways may play a major role in RA, we deve loped a severe combined immunodeficient (SCID) mouse model to study the mol ecular and cellular interaction between RA synovium and cartilage. Both RA synovium as well as isolated RA synovial fibroblasts were able to invade an d degrade normal human cartilage when coimplanted under the renal capsule o f the SCID mice. Subsequently, we used this model to study the effects of r etrovirus-based gene transfer of potentially inhibitory molecules into huma n RA synovial fibroblasts. Overexpression of interleukin (IL)-1 receptor an tagonist reduced perichondrocytic cartilage degradation, but did not affect the invasivity of RA synovial fibroblasts. Overexpression of tumor necrosi s factor (TNF)-alpha receptor p55 revealed only a marginal effect. However, overexpression of IL-10 showed a most remarkable inhibition of cartilage d estruction mediated by synovial fibroblasts. The SCID mouse model is a most useful tool not only to study the molecular basis of cartilage destruction , but also to evaluate novel approaches of gene therapy. (C) 1999 Prous Sci ence. All rights reserved.