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 sequence is found up-stream 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.
Yu
X
X
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06520-8061, USA.
Leconte
L
L
Martinez
J A
JA
Barnstable
C J
CJ
D000818:Animals; D004586:Electrophoresis; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000502:physiology; D009420:Nervous System / Q000196:embryology; D009424:Nervous System Physiological Phenomena; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D017299:Rod Opsins / Q000235:genetics*; D014157:Transcription Factors; D019076:Transgenes
D017299:Rod Opsins; D014157:Transcription Factors