Loss of myostatin expression alters fiber-type distribution and expression of myosin heavy chain isoforms in slow- and fast-type skeletal muscle.
Myostatin (Mstn) is a member of the transforming growth factor-beta family that negatively regulates skeletal muscle mass. Mstn knockout mice have greater skeletal muscle mass than wild-type littermates. We investigated the effect of Mstn on fiber type by comparing adult muscles from the murine Mstn knockout with wild-type controls. Based on myofibrillar ATPase staining, the soleus of Mstn knockout mice displays a larger proportion of fast type II fibers and a reduced proportion of slow type I fibers compared with wild-type animals. Based on staining for succinate dehydrogenase (SDH) activity, a larger proportion of glycolytic fibers and a reduced proportion of oxidative fibers occur in the extensor digitorum longus (EDL) of Mstn knockouts. These differences in distribution of fiber types are accompanied by differences in the expression of myosin heavy chain (MHC) isoforms. In both Mstn knockout soleus and EDL, larger numbers of faster MHC isoforms are expressed at the expense of slower isoforms when compared with wild-type littermates. Thus, the absence of Mstn in the knockout mouse leads to an overall faster and more glycolytic muscle phenotype. This muscle phenotype is likely a consequence of developmental processes, and inhibition of Mstn in adults does not cause a transformation to a more fast and glycolytic phenotype. Our findings suggest that myostatin has a critical role in regulating the formation, proliferation, or differentiation of fetal myoblasts and postnatal fibers.
Wyeth Department of Cardiovascular and Metabolic Diseases, 87 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA. sgirgenrath@netcape.net <sgirgenrath@netcape.net>
Stefan
S
Girgenrath
Kening
K
Song
Lisa-Anne
LA
Whittemore
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005260:Female; D015870:Gene Expression; D007536:Isomerism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016513:Mice, SCID; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D055435:Myostatin; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta; D018995:Myosin Heavy Chains