title: Mice lacking microRNA 133a  develop dynamin 2–dependent  centronuclear myopathy.
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.
authors: Department of Molecular Biology and 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75930-9148, USA. Ning.Liu@utsouthwestern.edu
authors: Ning
authors: N
authors: Liu
authors: Svetlana
authors: S
authors: Bezprozvannaya
authors: John M
authors: JM
authors: Shelton
authors: Madlyn I
authors: MI
authors: Frisard
authors: Matthew W
authors: MW
authors: Hulver
authors: Ryan P
authors: RP
authors: McMillan
authors: Yaru
authors: Y
authors: Wu
authors: Kevin A
authors: KA
authors: Voelker
authors: Robert W
authors: RW
authors: Grange
authors: James A
authors: JA
authors: Richardson
authors: Rhonda
authors: R
authors: Bassel-Duby
authors: Eric N
authors: EN
authors: Olson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D034285:Dynamin II / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D020914:Myopathies, Structural, Congenital; D010641:Phenotype; D020033:Protein Isoforms; D051381:Rats
chemical_list: D005227:Fatty Acids; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D020033:Protein Isoforms; D034285:Dynamin II