Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Sci China Life Sci. 2011 Feb;54(2):159-65. doi: 10.1007/s11427-010-4121-2. Epub 2011 Feb 14.
Myostatin is a member of the transforming growth factor-β (TGF-β) super-family and functions as a negative regulator of muscle growth. Binding of the specific receptor, Activin receptor IIB (Act RIIB), with myostatin or other related TGF-β members, could be inhibited by the activin-binding protein follistatin (Fst) in mammals. Overexpressing Fst in mouse skeletal muscle leads to muscle hypertrophy and hyperplasia. To determine if Fst has similar roles in fish, we generated transgenic zebrafish expressing high levels of zebrafish Fst1 using the promoter of the zebrafish skeletal muscle-specific gene, myosin, light polypeptide 2, skeletal muscle (Mylz2). Independent transgenic zebrafish lines exhibited elevated expression levels of myogenic regulatory genes MyoD and Pax7 in muscle cells. Adult Fst1 overexpressing transgenic zebrafish exhibited a slight body weight increase. The high level of Fst1 expression dramatically increased myofiber numbers in skeletal muscle, without significantly changing the fiber size. Our findings suggest that Fst1 overexpression can promote zebrafish muscle growth by enhancing myofiber hyperplasia.
肌肉生长抑制素（Myostatin）是转化生长因子-β（TGF-β）超家族的成员，作为肌肉生长的负调控因子发挥作用。在哺乳动物中，肌肉生长抑制素或其他相关 TGF-β 成员与特定受体激活素受体 IIB（Act RIIB）的结合可被激活素结合蛋白 follistatin（Fst）抑制。在小鼠骨骼肌中过表达 Fst 会导致肌肉肥大和增生。为了确定 Fst 是否在鱼类中具有相似的作用，我们使用斑马鱼骨骼肌特异性基因肌球蛋白轻链 2，骨骼肌肉（Mylz2）的启动子生成了高表达斑马鱼 Fst1 的转基因斑马鱼。独立的转基因斑马鱼系在肌肉细胞中表现出肌生成调节基因 MyoD 和 Pax7 的表达水平升高。Fst1 过表达的成年转基因斑马鱼体重略有增加。高水平的 Fst1 表达显著增加了骨骼肌中的肌纤维数量，而纤维大小没有明显变化。我们的研究结果表明，Fst1 的过表达可以通过增强肌纤维增生来促进斑马鱼的肌肉生长。
