Mice lacking microRNA 133a develop dynamin 2–dependent centronuclear myopathy
Ning Liu1, Svetlana Bezprozvannaya1, John M. Shelton2, Madlyn I. Frisard3, Matthew W. Hulver3, Ryan P. McMillan3, Yaru Wu3, Kevin A. Voelker3, Robert W. Grange3, James A. Richardson2, Rhonda Bassel-Duby1 and Eric N. Olson1
1Department of Molecular Biology and 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
3Department of Human Nutrition, Foods and Exercise, Virginia Tech University, Blacksburg, Virginia, USA.
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.
http://www.jci.org/articles/view/46267
