Myostatin-deficient mice exhibited larger muscle mass but generated significantly less specific force compared to wild-type mice, accompanied by mitochondrial depletion and altered fiber-type composition.
Does lack of myostatin improve muscle force generation in mice?
Although myostatin deficiency increases muscle mass, it compromises specific force production and oxidative characteristics, which may have implications for myostatin blockade therapies.
Absolute Event Rate: 9.4% vs 17.8%
p-value: p=<0.001
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 et al. (Fri,) conducted a other in Myostatin deficiency. Myostatin knockout vs. Wild-type mice was evaluated on Specific tetanic tension (N/g) in 7-month-old male EDL muscle (p=<0.001). Myostatin-deficient mice exhibited larger muscle mass but generated significantly less specific force compared to wild-type mice, accompanied by mitochondrial depletion and altered fiber-type composition.