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 cell receptor beta transgenic (TCRbetaL) mice that have a T cell repertoire that predisposes to the development of CIA were used. Classic genetic studies and microsatellite gene mapping were done in (SWR-betaL x DBA/1)F2 hybrid mice.

RESULTS

Besides TCRbeta, major histocompatibility complex class II, and Igh-C, at least 2 other genes are absolutely required for CIA development in these mice. A strict association of CIA with the presence of functional complement C5 allele (Hc1) was found, suggesting that Hc1 or a closely linked gene might be one of these essential genes.

CONCLUSION

This study provides new evidence of the pathogenetic role of complement C5 in CIA. Furthermore, these transgenic mice may facilitate molecular identification of other genes that predispose to CIA.