Establishment and phenotypic analysis of an Mstn knockout rat
Establishment and phenotypic analysis of an Mstn knockout rat
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Mstn基因敲除大鼠的建立及表型分析
DOI：
10.1016/j.bbrc.2016.06.030
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发表时间：
2016-08-12
影响因子：
3.1
通讯作者：
Yong, Weidong
中科院分区：
文献类型：
--
作者：
Gu, Hao;Cao, Yong;Yong, Weidong
肌生成抑制素（Myostatin，MSTs）是一种肌生成抑制剂，调节骨骼肌细胞的数量和大小。除了其生肌调节功能外，肌钙蛋白在脂肪组织的发育和代谢中起重要作用。本研究采用锌指核酸酶（ZFN）技术建立MMP3基因敲除大鼠模型，以进一步研究MMP3在代谢中的作用和机制。敲除具有移码突变，导致早期终止密码子和109个氨基酸的截短肽，而不是完整的376个氨基酸。不存在可检测的mRNA证实成功敲除了MIPs。相对于野生型（WT）同窝仔，敲除（KO）大鼠表现出显着更大的体重，体围和肌肉质量。然而，在握力方面没有观察到显著差异，表明Mc缺失导致更大的肌肉质量，但不是更大的肌纤维强度。此外，发现KO大鼠的体脂相对于WT同窝仔更少，这与先前在小鼠和牛中进行的研究一致。上述结果表明，Mackenzie敲除增加肌肉质量，同时降低脂肪含量，导致观察到的体重和体围增加。Mstn基因敲除大鼠模型为研究Mstn在代谢和Mstn相关肌肉肥大中的作用提供了一种新的手段。(C)2016年6月，作者。爱思唯尔公司出版
Myostatin (Mstn) is an inhibitor of myogenesis, regulating the number and size of skeletal myocytes. In addition to its myogenic regulatory function, Mstn plays important roles in the development of adipose tissues and in metabolism. In the present study, an Mstn knockout rat model was generated using the zinc finger nuclease (ZFN) technique in order to further investigate the function and mechanism of Mstn in metabolism. The knockout possesses a frame shift mutation resulting in an early termination codon and a truncated peptide of 109 amino acids rather than the full 376 amino acids. The absence of detectable mRNA confirmed successful knockout of Mstn. Relative to wild-type (WT) littermates, Knockout (KO) rats exhibited significantly greater body weight, body circumference, and muscle mass. However, no significant differences in grip force was observed, indicating that Mstn deletion results in greater muscle mass but not greater muscle fiber strength. Additionally, KO rats were found to possess less body fat relative to WT littermates, which is consistent with previous studies in mice and cattle. The aforementioned results indicate that Mstn knockout increases muscle mass while decreasing fat content, leading to observed increases in body weight and body circumference. The Mstn knockout rat model provides a novel means to study the role of Mstn in metabolism and Mstn-related muscle hypertrophy. (C) 2016 The Authors. Published by Elsevier Inc.