GENETIC-CONTROL OF SUSCEPTIBILITY TO COLLAGEN-INDUCED ARTHRITIS IN T-CELL RECEPTOR BETA-CHAIN TRANSGENIC MICE

Objective. To study the genes in the mouse background which predispose to the development of collagen-induced arthritis (CIA). Methods. T ce ll receptor beta transgenic (TCR beta L) mice that have a T cell reper toire that predisposes to the development of CU were used. Classic gen etic studies and microsatellite gene mapping were done in (SWR-beta L x DBA/1)F-2 hybrid mice. Results. Besides TCR beta, major histocompati bility complex class II, and Igh-C, at least 2 other genes are absolut ely required for CU development in these mice. A strict association of CU with the presence of functional complement C5 allele (Hc(1)) was f ound, suggesting that Hc(1) or a closely linked gene might be one of t hese essential genes. Conclusion. This study provides new evidence of the pathogenetic role of complement C5 in CIA. Furthermore, these tran sgenic mice may facilitate molecular identification of other genes tha t predispose to CIA.