Ret 1, a Cis‐Acting Element of the Rat Opsin Promoter, Can Direct Gene Expression in Rod Photoreceptors

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Abstract
The Ret 1 element, located at −136 to −110 in the rat opsin promoter, binds developmentally regulated retinal nuclear proteins. A similar sequence 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 mice. 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 promoter 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 binding specificity in vitro and were able to direct expression of a lacZ transgene in photoreceptors of all nine mouse lines obtained. In two lines, expression was also detected in the ganglion cell layer and the ciliary epithelium. In three lines, a characteristic pattern of expression was found in the nervous system in addition to the normal retinal expression. These results indicate that Ret 1 can and is necessary to drive gene expression in rod photoreceptors. Furthermore, our results suggest that Ret 1-like elements may also be important in the developing nervous system.

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