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人卵泡抑素-344的转基因表达增加了猪的骨骼肌质量。

The transgenic expression of human follistatin-344 increases skeletal muscle mass in pigs.

作者信息

Chang Fei, Fang Rui, Wang Meng, Zhao Xin, Chang Wen, Zhang Zaihu, Li Ning, Meng Qingyong

机构信息

State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.

China Agricultural University Pig Breeding Farm, Zhuo Zhou, Hebei, China.

出版信息

Transgenic Res. 2017 Feb;26(1):25-36. doi: 10.1007/s11248-016-9985-x. Epub 2016 Oct 27.

DOI:10.1007/s11248-016-9985-x
PMID:27787698
Abstract

Follistatin (FST), which was first found in the follicles of cattle and pigs, has been shown to be an essential regulator for muscle development. Mice that were genetically engineered to overexpress Fst specifically in muscle had at least twice the amount of skeletal muscle mass as controls; these findings are similar to earlier results obtained in myostatin-knockout mice. However, the role of follistatin in skeletal muscle development has yet to be clarified in livestock. Here, we describe transgenic Duroc pigs that exogenously express Fst specifically in muscle tissue. The transgenic pigs exhibited an increased proportion of skeletal muscle and a reduced proportion of body fat that were similar to those reported in myostatin-null cattle. The lean percentage of lean meat was significantly higher in the F1 generation of TG pigs (72.95 ± 1.0 %) than in WT pigs (69.18 ± 0.97 %) (N = 16, P < 0.05). Myofiber hypertrophy was also observed in the longissimus dorsi of transgenic pigs, possibly contributing to the increased skeletal muscle mass. Western blot analysis showed a significantly reduced level of Smad2 phosphorylation and an increased level of Akt phosphorylation in the skeletal muscle tissue of the transgenic pigs. Moreover, no cardiac muscle hypertrophy or reproductive abnormality was observed. These findings indicate that muscle-specific Fst overexpression in pigs enhances skeletal muscle growth, at least partly due to myofiber hypertrophy and providing a promising approach to increase muscle mass in pigs and other livestock.

摘要

卵泡抑素(FST)最初是在牛和猪的卵泡中发现的,已被证明是肌肉发育的重要调节因子。经过基因工程改造、在肌肉中特异性过表达Fst的小鼠,其骨骼肌质量至少是对照组的两倍;这些发现与早期在肌肉生长抑制素基因敲除小鼠中获得的结果相似。然而,卵泡抑素在牲畜骨骼肌发育中的作用尚未明确。在此,我们描述了在肌肉组织中特异性外源表达Fst的转基因杜洛克猪。转基因猪的骨骼肌比例增加,体脂比例降低,这与肌肉生长抑制素基因缺失牛的情况相似。转基因猪F1代的瘦肉率(72.95±1.0%)显著高于野生型猪(69.18±0.97%)(N = 16,P < 0.05)。在转基因猪的背最长肌中也观察到肌纤维肥大,这可能是骨骼肌质量增加的原因。蛋白质免疫印迹分析显示,转基因猪骨骼肌组织中Smad2磷酸化水平显著降低,Akt磷酸化水平升高。此外,未观察到心肌肥大或生殖异常。这些发现表明,猪中肌肉特异性Fst的过表达可促进骨骼肌生长,至少部分原因是肌纤维肥大,这为增加猪和其他牲畜的肌肉量提供了一种有前景的方法。

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本文引用的文献

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Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin.Follistatin 通过 Smad3 和 mTOR 独立调节肌肉肥大,不依赖于肌肉生长抑制素。
J Cell Biol. 2012 Jun 25;197(7):997-1008. doi: 10.1083/jcb.201109091. Epub 2012 Jun 18.
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High-level expression of bioactive recombinant human lysozyme in the milk of transgenic mice using a modified human lactoferrin BAC.利用改良的人乳铁蛋白 BAC 在转基因小鼠的乳汁中高水平表达具有生物活性的重组人溶菌酶。
Transgenic Res. 2012 Apr;21(2):407-14. doi: 10.1007/s11248-011-9536-4. Epub 2011 Jul 30.
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Regulation of muscle mass by follistatin and activins.
通过同源介导的末端连接实现的肌肉生长抑制素抑制剂位点特异性整合可增加猪的骨骼肌质量。
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miR299a-5p promotes renal fibrosis by suppressing the antifibrotic actions of follistatin.miR299a-5p 通过抑制卵泡抑素的抗纤维化作用促进肾纤维化。
Sci Rep. 2021 Jan 8;11(1):88. doi: 10.1038/s41598-020-80199-z.
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Transcriptomic profile of semitendinosus muscle of bulls of different breed and performance.不同品种和性能公牛半腱肌的转录组特征。
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Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA.通过纳米颗粒介导的肝内注射 Follistatin mRNA 增加小鼠的瘦肌肉质量。
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卵泡抑素和激活素对肌肉量的调节
Mol Endocrinol. 2010 Oct;24(10):1998-2008. doi: 10.1210/me.2010-0127. Epub 2010 Sep 1.
4
Follistatin gene delivery enhances muscle growth and strength in nonhuman primates.卵泡抑素基因递送增强了非人灵长类动物的肌肉生长和力量。
Sci Transl Med. 2009 Nov 11;1(6):6ra15. doi: 10.1126/scitranslmed.3000112.
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The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding.肌生成抑制蛋白:卵泡抑素288的结构:对受体利用和肝素结合的见解
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