Myostatin Knockout Mice Have Larger Muscle Fibers With Normal Function and Morphology.

Abstract

Introduction: We assessed whether muscle fibers in myostatin knockout (MSTN-/-) mice are just larger or also exhibit morphological, metabolic, and functional differences from MSTN+/+ mice.

Methods: We compared single fiber contractile properties and histological fiber properties in muscles from MSTN-/- and MSTN+/+ mice.

Results: Even though in permeabilized muscle fibers from the extensor digitorum longus and soleus muscle maximal force was higher (p < 0.001) there were no significant differences in specific power (power per unit volume), specific tension (force per cross-sectional area), maximal shortening velocity, or curvature of the force-velocity relationship between MSTN-/- and MSTN+/+ mice. In histological sections of the soleus muscle, fibers were larger (p < 0.001), but the succinate dehydrogenase staining intensity and capillary density did not differ significantly between MSTN-/- and MSTN+/+ mice, which was explicable by the larger number of capillaries around a fiber (p < 0.001). A model showed no significant differences in soleus muscle oxygenation.

Discussion: The larger force-generating capacity of fibers from MSTN-/- mice is explicable by the larger fiber cross-sectional area. The data indicate that muscle fibers from MSTN-/- mice are quantitatively, but not qualitatively different from muscle fibers from MSTN+/+ mice. Myostatin inhibition may help increase muscle mass in conditions accompanied by muscle weakness without a detrimental impact on muscle quality, but systemic side effects need to be considered.