Overexpression of the dominant-negative form of myostatin results in doubling of muscle-fiber number in transgenic medaka (Oryzias latipes)
Overexpression of the dominant-negative form of myostatin results in doubling of muscle-fiber number in transgenic medaka (Oryzias latipes)
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DOI：
10.1016/j.cbpa.2009.10.030
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发表时间：
2010-02-01
影响因子：
2.3
通讯作者：
Kinoshita, Masato
中科院分区：
文献类型：
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作者：
Sawatari, Etsuko;Seki, Ryoko;Kinoshita, Masato
除了改变基因修饰动物的表型外，转基因还具有促进分别了解特定表型和基因的发育和功能的各种机制的潜力。肌肉生长抑制素（MSTN）在哺乳动物中发生突变时与双肌形成有关，表明MSTN是骨骼肌形成的负调节因子。为了阐明MSTN等效物在鱼类肌肉形成中的作用，我们创建了一个只在骨骼肌中表达显性阴性MSTN的转基因medaka菌株d-rR-Tg（OIMA1-C315Y-MSTN-hrGFPII-FLAG）。转基因鱼在成年期（增生）骨骼肌纤维产量增加，但总肌肉质量没有改变。在胚胎发生过程中，观察到肌纤维异位积累和错位，可能是由于肌纤维肥大引起的。我们的研究结果表明，MSTN的功能是调节medaka骨骼肌适当生长所必需的。与哺乳动物不同，MSTN的功能丧失在medaka中未能诱导双肌形成。尽管MSTN功能在分类群中具有高度保守性。(C) 2009爱思唯尔公司版权所有。
in addition to altering the phenotypes of gene-modified animals, transgenesis also has the potential to facilitate access to the various mechanisms underlying the development and functioning of specific phenotypes and genes, respectively. Myostatin (MSTN) is implicated in double-muscling when mutated in mammals, indicating that MSTN is a negative regulator of skeletal muscle formation. In order to elucidate the role of an MSTN equivalent in fish muscle formation, we created a transgenic medaka strain that expresses dominant-negative MSTN exclusively in skeletal muscle, d-rR-Tg(OIMA1-C315Y-MSTN-hrGFPII-FLAG). The transgenic fish exhibited increased production of skeletal muscle fibers at the adult stage (hyperplasia), although gross muscle mass was not altered. During embryogenesis, ectopic accumulation and misalignment of muscle fibers, possibly due to muscle-fiber hypertrophy, were observed in the transgenic medaka. Our findings suggest that MSTN function is required for regulating the appropriate growth of skeletal muscle in medaka. Unlike in mammals, MSTN loss-of-function failed to induce double-muscling in medaka. despite the highly conserved nature of MSTN function among taxa. (C) 2009 Elsevier Inc. All rights reserved.