MSTN基因敲除抑制小鼠肌肉三羧酸循环和氧化磷酸化

发布时间：2018-03-27 19:10

本文选题：MSTN　切入点：线粒体　出处：《内蒙古大学》2017年硕士论文

【摘要】：肌肉抑制素(myostatin,MSTN)是TGF-β超家族的一员,广泛参与机体的生长发育调控。MSTN基因的自然突变会产生肌肉肥大的表型,在牛、羊、狗、小鼠以及人类中均有报道。MSTN通过负调控成肌生长因子,影响肌肉组织的发育和分化,同时,还参与调控肌纤维的代谢活动。本研究利用CRISPR/Cas9技术,获得了 MSTN第三外显子部分序列敲除的小鼠。以该小鼠为模型,检测MSTN敲除对小鼠基础代谢活动以及细胞线粒体功能的影响。结果如下:通过原核注射获得的MSTN-/-小鼠各器官中的MSTN基因表达量总体呈减少的趋势,小鼠体重显著增加,肌肉发达,表现出较明显的双肌现象。MSTN-/-小鼠基础代谢率下降,体温降低。MSTN基因的敲除显著影响了肌肉组织细胞中线粒体的功能,增强了线粒体中脂肪酸的β氧化,抑制了三羧酸循环和氧化磷酸化过程;参与线粒体合成的Tfam、Nrf1与Clpp等基因的表达显著上调,参与线粒体抗氧化的Sirt1和GSH等活性也显著提升。上述结果表明,MSTN基因敲除后,显著影响了小鼠的基础代谢,抑制了肌肉组织细胞线粒体的三羧酸循环和氧化磷酸化过程。
[Abstract]:Myostatin MSTN) is a member of the TGF- 尾 superfamily, extensively involved in the regulation of growth and development of the body. The natural mutation of the MSTN gene produces the phenotype of muscle hypertrophy in cattle, sheep, and dogs. It has been reported in mice and humans that MSTN affects the development and differentiation of muscle tissue through negative regulation of myogenic growth factor, and also participates in the regulation of muscle fiber metabolism. In this study, CRISPR/Cas9 technique was used. A mouse with partial knockout of exon 3 of MSTN was obtained. The effects of MSTN knockout on the basal metabolic activity and mitochondrial function in mice were determined. The results were as follows: the expression of MSTN gene in the organs of MSTN / R mice obtained by prokaryotic injection showed a decreasing trend, and the body weight of mice increased significantly. The muscle-developed mice showed obvious dimuscular phenomenon. The basal metabolic rate of mice was decreased, and the knockout of the .MSTN gene significantly affected the function of mitochondria and enhanced the 尾 -oxidation of fatty acids in the mitochondria. It inhibited the tricarboxylic acid cycle and oxidative phosphorylation, and up-regulated the expression of TfamNrf1 and Clpp genes involved in mitochondrial synthesis, as well as the activities of Sirt1 and GSH, which were involved in mitochondrial oxidation. It also inhibited the tricarboxylic acid cycle and oxidative phosphorylation of mitochondria in muscle histocytes.
【学位授予单位】：内蒙古大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：Q493

【参考文献】