Altered expression of the transcription factor Mef2c during retinal degeneration in Rpe65-/- mice

Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5933-40. doi: 10.1167/iovs.10-6978.


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 postnatal 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 and the expression 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 also indicate that Mef2c may act as a novel transcription factor involved in the development and the maintenance of photoreceptor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • MEF2 Transcription Factors
  • 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
  • cis-trans-Isomerases


  • Basic-Leucine Zipper Transcription Factors
  • Carrier Proteins
  • Eye Proteins
  • MEF2 Transcription Factors
  • Mef2c protein, mouse
  • Myogenic Regulatory Factors
  • Nr2e3 protein, mouse
  • Nrl protein, mouse
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • retinoid isomerohydrolase
  • cis-trans-Isomerases