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

Francisco J. Naya, Brian L. Black, Hai Wu, Rhonda S Bassel-Duby, James A Richardson, Joseph A Hill, Eric N Olson

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

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-1- 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.

Original languageEnglish (US)
Pages (from-to)1303-1309
Number of pages7
JournalNature Medicine
Volume8
Issue number11
DOIs
StatePublished - Nov 1 2002

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MEF2 Transcription Factors
Sudden Cardiac Death
Muscle
Genes
Chemical activation
Mitochondria
Gene expression
Protein Isoforms
Cells
Calcium
Sudden Death
Transgenes
Muscle Cells
Transcriptional Activation
Heart Ventricles
Dilatation
Myocardium
Gene Expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. / Naya, Francisco J.; Black, Brian L.; Wu, Hai; Bassel-Duby, Rhonda S; Richardson, James A; Hill, Joseph A; Olson, Eric N.

In: Nature Medicine, Vol. 8, No. 11, 01.11.2002, p. 1303-1309.

Research output: Contribution to journalArticle

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