Skeletal muscle myostatin mRNA expression is fiber-type specific and increases dining hindlimb unloading

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate grea ter skeletal muscle mass resulting from muscle fiber hypertrophy and hyperp lasia (McPherron, A. C., A. M. Lawler, and S.-J. Lee. Nature 387: 83-90, 19 97). Therefore, we hypothesized that, in normal mice, MSTN may act as a neg ative regulator of muscle mass. Specifically, we hypothesized that the pred ominately slow (type I) soleus muscle, which demonstrates greater atrophy t han the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would sh ow more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Su rprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus mus cle, which atrophied 42% by the 7th day of HU in female ICR mice. In contra st, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was signifi cantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the G ast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the sol eus is composed only of type I and IIa fibers, whereas the Gast/PLT express es type IId/x and IIb in addition to type I and IIa, it was necessary to pe rform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type) . A significant correlation (r = 0.725, P < 0.0005) was noted between the p ercentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it i s strongly associated with MHC isoform IIb expression in normal muscle.