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J Clin Invest. 2011 Aug;121(8):3258-68. doi: 10.1172/JCI46267.

Mice lacking microRNA 133a develop dynamin 2–dependent centronuclear myopathy.

Author information

  • 1Department of Molecular Biology and 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75930-9148, USA. Ning.Liu@utsouthwestern.edu

Abstract

MicroRNAs modulate cellular phenotypes by inhibiting expression of mRNA targets. In this study, we have shown that the muscle-specific microRNAs miR-133a-1 and miR-133a-2 are essential for multiple facets of skeletal muscle function and homeostasis in mice. Mice with genetic deletions of miR-133a-1 and miR-133a-2 developed adult-onset centronuclear myopathy in type II (fast-twitch) myofibers, accompanied by impaired mitochondrial function, fast-to-slow myofiber conversion, and disarray of muscle triads (sites of excitation- contraction coupling). These abnormalities mimicked human centronuclear myopathies and could be ascribed, at least in part, to dysregulation of the miR-133a target mRNA that encodes dynamin 2, a GTPase implicated in human centronuclear myopathy. Our findings reveal an essential role for miR-133a in the maintenance of adult skeletal muscle structure, function, bioenergetics, and myofiber identity; they also identify a potential modulator of centronuclear myopathies.

PMID:
21737882
[PubMed - indexed for MEDLINE]
PMCID:
PMC3148737
Free PMC Article

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