Lack of myostatin results in excessive muscle growth but impaired force generati

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Proc Natl Acad Sci U S A. 2007 Jan 31

Lack of myostatin results in excessive muscle growth but impaired

force generation.

Amthor H, Macharia R, Navarrete R, Schuelke M, Brown SC, Otto A,

Voit T, Muntoni F, Vrbova G, Partridge T, Zammit P, Bunger L, Patel

K.

Department of Paediatrics, University Hospital of Essen, 45122

Essen, Germany;

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.