title: Molecular, cellular, and muscle strip mechanics of the mdx mouse diaphragm.
abstract: Duchenne muscular dystrophy (DMD) is a lethal disorder caused by defects in the dystrophin gene, which leads to respiratory or cardiac muscle failure. Lack of dystrophin predisposes the muscle cell sarcolemmal membrane to mechanical damage. However, the role of myosin in this muscle weakness has been poorly addressed. In the current study, in addition to measuring the velocity of actin filament propulsion (υmax) of mdx myosin molecules purified from 3- and 12-mo-old control (C57Bl/10) and mdx (C57Bl/10mdx) mouse diaphragms, we also measured myosin force production. Furthermore, we measured cellular and muscle strip force production at three mo of age. Stress (force/cross-sectional area) was smaller for mdx than control at the muscle strip level but was not different at the single fiber level. υmax of mdx myosin was not different from control at either 3 or 12 mo nor was their relative myosin force. The type I and IIb myosin heavy chain composition was not different between control and mdx diaphragms at 3 or 12 mo. These results suggest that the myosin function, as well as the single fiber mechanics, do not underlie the weakness of the mdx diaphragm. This weakness was only observed at the level of the intact muscle bundle and could not be narrowed down to a specific mechanical impairment of its individual fibers or myosin molecules.
authors: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada.
authors: Genevieve
authors: G
authors: Bates
authors: Sara
authors: S
authors: Sigurdardottir
authors: Linda
authors: L
authors: Kachmar
authors: Nedjma B
authors: NB
authors: Zitouni
authors: Andrea
authors: A
authors: Benedetti
authors: Basil J
authors: BJ
authors: Petrof
authors: Dilson
authors: D
authors: Rassier
authors: Anne-Marie
authors: AM
authors: Lauzon
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003964:Diaphragm / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009218:Myosins / Q000737:chemistry / Q000502:physiology*; D059748:Proteolysis
chemical_list: D009218:Myosins
keywords: duchenne muscular dystrophy; dystrophin; in vitro motility assay