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- Title
Mice lacking microRNA 133a develop dynamin 2–dependent centronuclear myopathy.
- Authors
Ning Liu; Bezprozvannaya, Svetlana; Shelton, John M.; Frisard, Madlyn I.; Hulver, Matthew W.; cMillan, Ryan P.; Wu, Yaru; Voelker, Kevin A.; Grange, Robert W.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.; Liu, Ning; McMillan, Ryan P
- 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.
- Subjects
LABORATORY mice; MUSCLE diseases; PHENOTYPES; GENETIC mutation; BIOENERGETICS; DYNAMIN (Genetics); RNA metabolism; RNA physiology; ANIMAL experimentation; BIOLOGICAL models; COMPARATIVE studies; FATTY acids; HYDROLASES; RESEARCH methodology; MEDICAL cooperation; MICE; MITOCHONDRIA; PROTEINS; RATS; RESEARCH; RNA; EVALUATION research; SKELETAL muscle
- Publication
Journal of Clinical Investigation, 2011, Vol 121, Issue 8, p3258
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI46267