title: Myopathic changes in murine skeletal muscle lacking synemin.
abstract: Diseases of striated muscle linked to intermediate filament (IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle.
authors.affiliation: Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland;
authors.forename: Karla P
authors.initials: KP
authors.lastname: García-Pelagio
authors.affiliation: Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland;
authors.forename: Joaquin
authors.initials: J
authors.lastname: Muriel
authors.affiliation: Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland;
authors.forename: Andrea
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: Program in Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland;
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Desmond
authors.affiliation: Department of Orthopaedics, School of Medicine, University of Maryland, Baltimore, Maryland;
authors.forename: Richard M
authors.initials: RM
authors.lastname: Lovering
authors.affiliation: Merrick School of Business, University of Baltimore, Baltimore, Maryland; and.
authors.forename: Linda
authors.initials: L
authors.lastname: Lund
authors.affiliation: College of Sciences and Health Professions, Cleveland State University, Cleveland, Ohio.
authors.forename: Meredith
authors.initials: M
authors.lastname: Bond
authors.affiliation: Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland; rbloch@umaryland.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bloch
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D054974:Costameres / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D007381:Intermediate Filament Proteins / Q000172:deficiency* / Q000235:genetics; D007537:Isometric Contraction; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018763:Muscle Fatigue; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012420:Running; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology
chemical_list: D007381:Intermediate Filament Proteins; C491443:synemin protein, mouse
keywords: biomechanical properties; costameres; cytoskeleton; desmin; elastimetry