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徐弘毅,卢芸,李远远,等.HIF-1α对颏舌肌发育和肌纤维类型的影响[J].同济大学学报（医学版）,2017,38(2):1-4. [点击复制]
XU Hong-yi,LU Yun,LI Yuan-yuan,et al.Effect of HIF-1α on muscle fiber differentiation in mice[J].同济大学学报（医学版）,2017,38(2):1-4. [点击复制]

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HIF-1α对颏舌肌发育和肌纤维类型的影响
徐弘毅,卢芸,李远远,刘月华
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(同济大学附属口腔医院正畸科,上海 200072;上海牙组织修复与再生工程技术研究中心,上海 200072;上海市口腔病防治院正畸科,上海 200001)

摘要:

目的研究低氧诱导因子-1α(hypoxia-inducible factor-1α, HIF-1α)对骨骼肌发育及肌纤维分型的影响。方法将HIF^flox/-转基因小鼠和骨骼肌环化重组酶(muscle creatine kinase-cyclization recombination enzyme, MCK-Cre)转基因小鼠交配,子代中获得HIF^flox/-Cre⁺小鼠互交,得到骨骼肌HIF-1α条件性敲降的HIFflox/floxCre⁺基因型小鼠(C₅₇BL/6J),取新生小鼠尾尖与骨骼肌组织鉴定基因型及敲降效率。随机选取HIF-1α敲降小鼠(KO)和野生型小鼠(WT)各10只,取颏舌肌组织总RNA,使用荧光定量PCR检测4种肌纤维类型(Ⅰ、Ⅱa、Ⅱb、Ⅱx)在不同基因型小鼠骨骼肌中的表达差异。结果 HIF-1α在基因敲除小鼠(KO)的骨骼肌中的表达量较野生型小鼠(WT)有明显降低(P<0.05)。相对于野生型小鼠(WT),基因敲除小鼠(KO)颏舌肌的Ⅰ、Ⅱa、Ⅱx型肌纤维表达量有降低趋势,而Ⅱb型纤维表达量有升高趋势。结论 Cre-loxP系统成功构建骨骼肌特异性敲除HIF-1α的转基因小鼠模型。HIF-1α在成肌分化过程中能够促进肌纤维Ⅰ、Ⅱa、Ⅱx分化,抑制Ⅱb纤维分化。

关键词: 低氧诱导因子-1α 条件性基因敲除骨骼肌纤维小鼠

DOI：10.16118/j.1008-0392.2017.02.001

投稿时间：2017-01-20

基金项目:国家自然科学基金(81271192)

Effect of HIF-1α on muscle fiber differentiation in mice

XU Hong-yi,LU Yun,LI Yuan-yuan,LIU Yue-hua

(Dept.of Orthodontics, Hospital of Stomatology, Tongji University, Shanghai 200072, China;Research Center of Tooth Restoration and Regeneration Engineering, Shanghai 200072, China;Dept.of Orthodontics, Shanghai Stomatology Hospital, Shanghai 200001, China)

Abstract:

Objective To investigate the biological effects of hypoxia-inducible factor-1α (HIF-1α) on skeletal muscle differentiation with conditional knockout mice. Methods HIFflox/floxCre⁺ gene type were obtained by inbreeding HIFflox/- transgenic mice and muscle creatine kinase-cyclization recombination enzyme(MCK-Cre) transgenic mice. The expression of HIF-1α in skeletal muscle was identified by Real-Time PCR methods. Ten mice were randomly selected from each group of the mice named KO and WT. The expressions of muscle fiber type Ⅰ,Ⅱa,Ⅱb andⅡx were detected by real-time PCR. Results Compared with WT mice, the expression of HIF-1α in KO mice was significantly reduced (P＜0.05). In KO mice, there was a slight decrease inⅠ,Ⅱa,Ⅱx fiber types but an increase inⅡb fiber type. Conclusion The HIF-1α conditional knockout mice model has been successfully established from Cre-loxP system. HIF-1α can enhance typesⅠ, Ⅱa and Ⅱx fiber generation during the process of myogenic differentiation and suppresse Ⅱb fiber generation.

Key words: HIF-1α conditional gene knock-out mice skeletal muscle fiber mice