OVEREXPRESSION OF FRA-2 IN TRANSGENIC MICE PERTURBS NORMAL EYE DEVELOPMENT

The major components of transcription factor AP-1 (Activator Protein 1 ) are encoded by the two families of genes related to the proto-oncoge nes c-fos and c-jun. The fos-related antigen-2 (fra-2) gene is the mos t recently described member of the Fos family. To determine the oncoge nic potential of fra-2, transgenic mice were generated which over-expr ess fra-2 in a number of tissues. No tumours were evident in any trans genic mice up to 18 months of age, although eye development was severe ly disrupted in these animals. Corneal abnormalities could be observed histologically as early as embryonic day 15.5 and eyelid fusion faile d to occur. Adult eyes were characterized by generalized anterior segm ent dysgenesis similar to that previously reported in transgenic mice over-expressing transforming growth factor alpha (TGF alpha), and occa sionally microphthalmia. Expression of fra-2 was shown to increase fol lowing TGF alpha. treatment of cells in vitro, suggesting that AP-1 co mplexes containing Fra-2 contribute to TGF alpha signalling events.