Fra-1 replaces c-Fos-dependent functions in mice

Structure-function analysis as well as studies with knock-out and transgeni c mice have assigned distinct functions to c-Fos and Fra-1, two components of the transcription factor AP-1 (activator protein-1). To test whether Fra -1 could substitute for c-Fos, we generated knock-in mice that express Fra- 1 in place of c-Fos. Fra-1 rescues c-Fos-dependent functions such as bone d evelopment and light-induced photoreceptor apoptosis. Importantly, rescue, of bone cell differentiation, but not photoreceptor apoptosis, is gene-dosa ge dependent. Moreover, Fra-1 fails to substitute for c-Fos in inducing exp ression of target genes in fibroblasts. These results show that c-Fos and P ra-l have maintained functional equivalence during vertebrate evolution.