Maximal P o was reached at 100 Hz in both Mstn −/− and C57BL/6 wild-type muscles and did not increase with stimulation at higher frequencies. The maximal isometric twitch force ( P t) and tetanic force ( P o) of extensor digitorum longus (EDL) muscles of 7-month-old male Mstn −/− and age-matched C57BL/6 wild-type mice are presented in Table 1 and Fig.
#DRFONE ADOBE BT I CK SERIES#
To examine the relationship between muscle size and improved function in Mstn −/− mice, we first performed a series of tests of force generation. It is reported, however, that myostatin-deficient mice do not suffer from muscle fiber damage when subjected to brief periods of exercise ( 11). Furthermore, cattle with hereditary muscular hypertrophy (double-muscled cattle), many of which have been shown to harbor mutations in the myostatin ( Mstn) gene, are actually prone to muscle damage after mild exercise ( 7– 10). Doubts of this sort are indirectly supported by the observation that this increase in muscle mass is not accompanied by a proportionate increase in muscle force ( 5, 6). Such views may have neglected a critical evaluation of the functional aspects of muscle hypertrophy induced by the absence of myostatin. In some respects, this is paradoxical, because muscularity has been positively associated with vigor and reproductive fitness. This finding, together with the extremely rare incidence of spontaneous mutations within the gene ( 3, 4), points to biological advantage and associated evolutionary constraints on muscle size by this pathway. The myostatin gene encodes a member of the TGF-β family of signaling molecules and has been highly conserved throughout vertebrate evolution ( 2).
Lack of myostatin function results in the excessive growth of skeletal muscle, demonstrating the existence of a powerful mechanism to control muscle size in normal individuals ( 1). Overall, our results suggest that lack of myostatin compromises force production in association with loss of oxidative characteristics of skeletal muscle. Moreover, the ratio of mitochondrial DNA to nuclear DNA and mitochondria number were decreased in myostatin-deficient muscle, suggesting a mitochondrial depletion. This change was also accompanied by a significant increase in type IIB fibers containing tubular aggregates. 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.
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. 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). 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.
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