Carlson C J, Booth F W, Gordon S E
Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Am J Physiol. 1999 Aug;277(2 Pt 2):R601-6. doi: 10.1152/ajpregu.1999.277.2.r601.
Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform 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 percentage 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 is strongly associated with MHC isoform IIb expression in normal muscle.
缺乏功能性肌生成抑制素（MSTN）基因的转基因小鼠表现出更大的骨骼肌质量，这是由肌纤维肥大和增生所致（麦克弗伦，A.C.，A.M.劳勒，以及S.-J.李。《自然》387: 83 - 90，1997）。因此，我们推测，在正常小鼠中，MSTN可能作为肌肉质量的负调节因子。具体而言，我们推测，主要为慢肌（I型）的比目鱼肌，其萎缩程度比快肌（II型）的腓肠肌 - 跖肌复合体（Gast/PLT）更严重，在后肢卸载（HU）过程中，其MSTN mRNA丰度会有更高的升高。令人惊讶的是，在负重或HU的比目鱼肌中未检测到MSTN mRNA，在雌性ICR小鼠中，到HU第7天时，该比目鱼肌萎缩了42%。相反，MSTN mRNA存在于负重的Gast/PLT肌肉中，在HU第1天显著升高（67%），但在第3天和第7天未升高。然而，到HU第7天时，Gast/PLT肌肉仅萎缩了17%。由于比目鱼肌仅由I型和IIa型纤维组成，而Gast/PLT除了I型和IIa型外还表达IId/x型和IIb型，因此有必要更仔细地分析MSTN mRNA水平与肌球蛋白重链（MHC）同工型表达（作为纤维类型的标志物）之间的关系。在小鼠后肢的几块肌肉中，MHC同工型IIb表达的百分比与MSTN mRNA丰度之间存在显著相关性（r = 0.725，P < 0.0005）。这些结果表明，MSTN表达与HU诱导的肌肉萎缩没有强烈关联；然而，它与正常肌肉中的MHC同工型IIb表达密切相关。
