Mice lacking microRNA 133a develop dynamin 2-dependent centronuclear myopathy

Ning Liu, Svetlana Bezprozvannaya, John M. Shelton, Madlyn I. Frisard, Matthew W. Hulver, Ryan P. McMillan, Yaru Wu, Kevin A. Voelker, Robert W. Grange, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

90 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3258-3268
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number8
DOIs
StatePublished - Aug 1 2011

ASJC Scopus subject areas

  • Medicine(all)

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    Liu, N., Bezprozvannaya, S., Shelton, J. M., Frisard, M. I., Hulver, M. W., McMillan, R. P., Wu, Y., Voelker, K. A., Grange, R. W., Richardson, J. A., Bassel-Duby, R., & Olson, E. N. (2011). Mice lacking microRNA 133a develop dynamin 2-dependent centronuclear myopathy. Journal of Clinical Investigation, 121(8), 3258-3268. https://doi.org/10.1172/JCI46267