title: Lack of myostatin results in excessive muscle growth but impaired force generation.
abstract: The lack of myostatin promotes growth of skeletal muscle, and blockade of its activity has been proposed as a treatment for various muscle-wasting disorders. Here, we have examined two independent mouse lines that harbor mutations in the myostatin gene, constitutive null (Mstn(-/-)) and compact (Berlin High Line, BEH(c/c)). We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles. In addition, Mstn(-/-) muscle contracted and relaxed faster during a single twitch and had a marked increase in the number of type IIb fibers relative to wild-type controls. This change was also accompanied by a significant increase in type IIB fibers containing tubular aggregates. Moreover, the ratio of mitochondrial DNA to nuclear DNA and mitochondria number were decreased in myostatin-deficient muscle, suggesting a mitochondrial depletion. Overall, our results suggest that lack of myostatin compromises force production in association with loss of oxidative characteristics of skeletal muscle.
authors.affiliation: Department of Paediatrics, University Hospital of Essen, Essen, Germany. helge.amthor@psl.aphp.fr
authors.forename: Helge
authors.initials: H
authors.lastname: Amthor
authors.forename: Raymond
authors.initials: R
authors.lastname: Macharia
authors.forename: Roberto
authors.initials: R
authors.lastname: Navarrete
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.forename: Susan C
authors.initials: SC
authors.lastname: Brown
authors.forename: Anthony
authors.initials: A
authors.lastname: Otto
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Gerta
authors.initials: G
authors.lastname: Vrbóva
authors.forename: Terence
authors.initials: T
authors.lastname: Partridge
authors.forename: Peter
authors.initials: P
authors.lastname: Zammit
authors.forename: Lutz
authors.initials: L
authors.lastname: Bunger
authors.forename: Ketan
authors.initials: K
authors.lastname: Patel
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000502:physiology / Q000503:physiopathology*; D055435:Myostatin; D010084:Oxidation-Reduction; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta