Lack of myostatin results in excessive muscle growth but impaired force generation.
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.
Amthor
Helge
H
Department of Paediatrics, University Hospital of Essen, Essen, Germany. helge.amthor@psl.aphp.fr
Macharia
Raymond
R
Navarrete
Roberto
R
Schuelke
Markus
M
Brown
Susan C
SC
Otto
Anthony
A
Voit
Thomas
T
Muntoni
Francesco
F
Vrbóva
Gerta
G
Partridge
Terence
T
Zammit
Peter
P
Bunger
Lutz
L
Patel
Ketan
K
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
C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta