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

Degens, Hans ORCID: https://orcid.org/0000-0001-7399-4841, Patel, Ketan and Matsakas, A (2025) Myostatin Knockout Mice Have Larger Muscle Fibers With Normal Function and Morphology. Muscle & Nerve. ISSN 0148-639X

Published Version Available under License Creative Commons Attribution. Download (1MB)

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.