Article: article d'un périodique ou d'un magazine.
Altered expression of the transcription factor Mef2c during retinal degeneration in Rpe65-/- mice.
Investigative Ophthalmology and Visual Science
Date de publication
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Purpose. To investigate the role of the myocyte enhancer factor 2 (Mef2) transcription factor family in retinal diseases, Mef2c expression was assessed during retinal degeneration in the Rpe65(-/-) mouse model of Leber's congenital amaurosis (LCA). Mef2c-dependent expression of photoreceptor-specific genes was further addressed. Methods. Expression of Mef2 members was analyzed by oligonucleotide microarray, quantitative PCR (qPCR) and in situ hybridization. Mef2c-dependent transcriptional activity was assayed by luciferase assay in HEK293T cells. Results. Mef2c was the only Mef2 member markedly downregulated during retinal degeneration in Rpe65(-/-) mice. Mef2c mRNA level was decreased by more than 2 fold at 2 and 4 months and by 3.5 fold at 6 months in retinas of Rpe65(-/-) mice. Downregulation of Mef2c at the protein level was confirmed in Rpe65(-/-) retinas. The decrease in Mef2c mRNA levels in the developing Rpe65(-/-) retinas, from post-natal day (P)13 onward, was concomitant with the decreased expression of the rod-specific transcription factors Nrl and Nr2e3. Nrl was further shown to drive Mef2c transcriptional activity, supporting a physiological role for Mef2c in the retina. In addition, Mef2c appeared to act as a transcriptional repressor of its own expression, as well as those of the retina-specific retinal G-protein coupled receptor (Rgr), rhodopsin and M-opsin genes. Conclusions. These findings highlight the early altered regulation of the rod-specific transcriptional network in Rpe65-related disease. They further indicate that Mef2c may act as a novel transcription factor involved in the development and the maintenance of photoreceptor cells.
Animals, Base Sequence, Basic-Leucine Zipper Transcription Factors/genetics, Carrier Proteins/genetics, Down-Regulation/physiology, Eye Proteins/genetics, Gene Expression/physiology, HEK293 Cells, Humans, Leber Congenital Amaurosis/genetics, Leber Congenital Amaurosis/physiopathology, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Molecular Sequence Data, Myogenic Regulatory Factors/genetics, Myogenic Regulatory Factors/metabolism, Oligonucleotide Array Sequence Analysis, Orphan Nuclear Receptors/genetics, Promoter Regions, Genetic/physiology, RNA, Messenger/metabolism, Retinal Degeneration/genetics, Retinal Degeneration/physiopathology, Retinal Rod Photoreceptor Cells/metabolism, Retinal Rod Photoreceptor Cells/physiology, Transcription, Genetic/physiology
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