title: The SCID mouse--a novel experimental model for gene therapy in human rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is characterized by a progressive destruction of joints accompanied by synovial hyperplasia, inflammation and autoimmune phenomena. RA is a common disease, but current animal models resemble human RA only to a limited extent. As recent experimental approaches support the concept that T-cell-independent pathways may play a major role in RA, we developed a severe combined immunodeficient (SCID) mouse model to study the molecular and cellular interaction between RA synovium and cartilage. Both RA synovium as well as isolated RA synovial fibroblasts were able to invade and degrade normal human cartilage when coimplanted under the renal capsule of the SCID mice. Subsequently, we used this model to study the effects of retrovirus-based gene transfer of potentially inhibitory molecules into human RA synovial fibroblasts. Overexpression of interleukin (IL)-1 receptor antagonist reduced perichondrocytic cartilage degradation, but did not affect the invasiveness of RA synovial fibroblasts. Overexpression of tumor necrosis factor (TNF)-alpha receptor p55 revealed only a marginal effect. However, overexpression of IL-10 showed a most remarkable inhibition of cartilage destruction 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.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: S
authors.initials: S
authors.lastname: Gay