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

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作者：

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

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摘要：

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.

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关键词：

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