Establishment and phenotypic analysis of an Mstn knockout rat.
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.
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Hao
H
Gu
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China; Experimental Medicine Center, The First Affiliated Hospital of Sichuan Medical University, Sichuan 646000, China.
Yong
Y
Cao
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Bin
B
Qiu
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Zhiqiang
Z
Zhou
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Ran
R
Deng
Experimental Medicine Center, The First Affiliated Hospital of Sichuan Medical University, Sichuan 646000, China.
Zhuang
Z
Chen
The Key Laboratory of Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Hohhot 010021, China.
Rongfeng
R
Li
The Key Laboratory of Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Hohhot 010021, China.
Xueling
X
Li
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Qiang
Q
Wei
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130122, China. Electronic address: xiaxzh@cae.cn.
Xianzhu
X
Xia
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China. Electronic address: wyong@cnilas.org.
Weidong
W
Yong
D000273:Adipose Tissue; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005260:Female; D008297:Male; D055435:Myostatin / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D055647:Rats, Transgenic
C525913:Mstn protein, rat; D055435:Myostatin
Knockout rats; Mstn; Muscle development; TGF-β