RET-1, A CIS-ACTING ELEMENT OF THE RAT OPSIN PROMOTER, CAN DIRECT GENE-EXPRESSION IN ROD PHOTORECEPTORS

The Ret 1 element, located at -136 to -110 in the rat opsin promoter, binds developmentally regulated retinal nuclear proteins. A similar se quence is found upstream of opsin genes, from humans to Drosophila, as well as many other photoreceptor-specific genes. The function of the Ret 1 element was tested both in vitro and in two sets of transgenic m ice, A mutated Ret 1 element did not bind retinal nuclear proteins in vitro. The same mutations in an otherwise normal 1.9-kb rat opsin prom oter failed to drive expression of a lacZ reporter gene in nine of 12 lines, In the three other lines, expression in photoreceptors was very faint. Four tandem copies of the Ret 1 element maintained the Ret 1 b inding specificity in vitro and were able to direct expression of a la cZ transgene in photoreceptors of all nine mouse lines obtained. In tw o lines, expression was also detected in the ganglion cell layer and t he ciliary epithelium. In three lines, a characteristic pattern of exp ression was found in the nervous system in addition to the normal reti nal expression. These results indicate that Ret 1 can and is necessary to drive gene expression in rod photoreceptors. Furthermore, our resu lts suggest that Ret 1-like elements may also be important in the deve loping nervous system.