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Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor.

The four MEF2 transcription factors (MEF2A, -B, -C, and -D) regulate differentiation and calcium-dependent gene expression in muscle cells. We generated mice deficient in MEF2A, the predominant Mef2 gene product expressed in post-natal cardiac muscle. Most mice lacking Mef2a died suddenly within the first week of life and exhibited pronounced dilation of the right ventricle, myofibrillar fragmentation, mitochondrial disorganization and activation of a fetal cardiac gene program. The few Mef2a(-/-) mice that survived to adulthood also showed a deficiency of cardiac mitochondria and susceptibility to sudden death. Paradoxically, MEF2 transcriptional activity, revealed by the expression of a MEF2-dependent transgene, was enhanced in the hearts of Mef2a-mutant mice, reflecting the transcriptional activation of residual MEF2D. These findings reveal specific roles for MEF2A in maintaining appropriate mitochondrial content and cyto-architectural integrity in the post-natal heart and show that other MEF2 isoforms cannot support these activities.

Pubmed ID: 12379849

Authors

  • Naya FJ
  • Black BL
  • Wu H
  • Bassel-Duby R
  • Richardson JA
  • Hill JA
  • Olson EN

Journal

Nature medicine

Publication Data

November 4, 2002

Associated Grants

None

Mesh Terms

  • Animals
  • DNA-Binding Proteins
  • Death, Sudden, Cardiac
  • Electrophoretic Mobility Shift Assay
  • MEF2 Transcription Factors
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mitochondria, Heart
  • Myogenic Regulatory Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors