本文選題：MSTN　切入點：線粒體　出處：《內(nèi)蒙古大學》2017年碩士論文

【摘要】：肌肉抑制素(myostatin,MSTN)是TGF-β超家族的一員,廣泛參與機體的生長發(fā)育調(diào)控。MSTN基因的自然突變會產(chǎn)生肌肉肥大的表型,在牛、羊、狗、小鼠以及人類中均有報道。MSTN通過負調(diào)控成肌生長因子,影響肌肉組織的發(fā)育和分化,同時,還參與調(diào)控肌纖維的代謝活動。本研究利用CRISPR/Cas9技術,獲得了 MSTN第三外顯子部分序列敲除的小鼠。以該小鼠為模型,檢測MSTN敲除對小鼠基礎代謝活動以及細胞線粒體功能的影響。結果如下:通過原核注射獲得的MSTN-/-小鼠各器官中的MSTN基因表達量總體呈減少的趨勢,小鼠體重顯著增加,肌肉發(fā)達,表現(xiàn)出較明顯的雙肌現(xiàn)象。MSTN-/-小鼠基礎代謝率下降,體溫降低。MSTN基因的敲除顯著影響了肌肉組織細胞中線粒體的功能,增強了線粒體中脂肪酸的β氧化,抑制了三羧酸循環(huán)和氧化磷酸化過程;參與線粒體合成的Tfam、Nrf1與Clpp等基因的表達顯著上調(diào),參與線粒體抗氧化的Sirt1和GSH等活性也顯著提升。上述結果表明,MSTN基因敲除后,顯著影響了小鼠的基礎代謝,抑制了肌肉組織細胞線粒體的三羧酸循環(huán)和氧化磷酸化過程。
[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.
【學位授予單位】：內(nèi)蒙古大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：Q493

【參考文獻】

相關期刊論文 前1條

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本文編號：1672851