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首页> 外文期刊>International Journal of Molecular Sciences >Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice
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Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice

机译：猪肌生长抑制素错义突变体的过表达导致转基因雄性和雌性小鼠骨骼肌生长的性别差异。

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Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.
机译：肌生长抑制素是一种转化生长因子-β家族成员，是骨骼肌发育和生长的负调节剂。皮埃蒙特的牛品种具有错义突变，导致成熟的肌肉生长抑制素蛋白（C313Y）中的半胱氨酸替换为酪氨酸。肌生长抑制素的这种功能丧失突变导致牛的双重肌肉表型。肌生长抑制素原肽是肌生长抑制素活性的抑制剂，被认为是刺激家畜肌肉生长的潜在药物。在这项研究中，我们分别产生了过表达猪肌生长抑制素错义突变体（pmMS），C313Y和野生型猪肌生长抑制素前肽（ppMS）的转基因小鼠，以研究它们对小鼠肌肉生长的影响。在pmMS和ppMS转基因雌性小鼠中以及在ppMS转基因雄性小鼠中均观察到肌肉生长增强。但是，在pmMS转基因雄性小鼠中没有观察到肌肉生长增强。为了探讨为什么在pmMS和ppMS转基因雄性小鼠之间的肌肉生长存在如此大的差异，通过Western blot检测了雄激素受体（AR）突变体AR45的表达水平。结果表明，AR45表达在pmMS转基因雄性小鼠中显着增加，而在ppMS转基因雄性小鼠中显着降低。我们的数据表明pmMS和ppMS均在肌肉生长调节中充当肌生长抑制素抑制剂，但pmMS在雄性小鼠中的作用因AR45表达增加而被逆转。这些结果为将来通过基因操纵肌生长抑制素表达或调节肌生长抑制素活性来改善猪肉质量提供了有用的见识和基础理论。

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