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.[1]References
- Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Naya, F.J., Black, B.L., Wu, H., Bassel-Duby, R., Richardson, J.A., Hill, J.A., Olson, E.N. Nat. Med. (2002) [Pubmed]
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