Transgenic overexpression of miR-133a in skeletal muscle.

Transgenic overexpression of miR-133a in skeletal muscle.
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DOI:
10.1186/1471-2474-12-115
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发表时间:
2011-05-26
影响因子:
2.3
通讯作者:
Wang DZ
Wang DZ
中科院分区:
医学3区
文献类型:
--
作者:
Deng Z;Chen JF;Wang DZ

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MicroRNA (miRNA) 是一类长度约为 22 个核苷酸的非编码调节 RNA。 miRNA 主要通过与其调节目标 mRNA 的 3' 非翻译区 (UTR) 相关联,在转录后调节基因表达。最近的工作已经开始揭示 miRNA 在广泛的生物过程中的作用,包括细胞增殖、分化和凋亡。许多 miRNA 在心脏和骨骼肌中表达,并且 miRNA 表达失调与肌肉相关疾病相关。我们之前报道过,肌肉特异性 miR-1 和 miR-133 的表达在骨骼肌分化过程中被诱导,并且 miR-1 和 miR-133 在体外成肌细胞增殖和分化中发挥核心调节作用。在这项研究中,我们测量了 mdx 小鼠骨骼肌中 miRNA 的表达,mdx 小鼠是人类肌营养不良症的动物模型。我们还培育了在骨骼肌中过度表达 miR-133a 的转基因小鼠。我们检测了 mdx 小鼠骨骼肌中 miRNA 的表达。我们发现 mdx 小鼠骨骼肌中肌肉 miRNA(包括 miR-1a、miR-133a 和 miR-206)的表达上调。为了进一步研究miR-133a在体内骨骼肌中的功能,我们创建了几个独立的转基因创始系。令人惊讶的是,miR-133a 转基因小鼠的骨骼肌发育和功能似乎不受影响。我们的结果表明 miR-133a 对于骨骼肌的正常发育和功能是不可或缺的。
MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of ~22 nucleotides in length. miRNAs regulate gene expression post-transcriptionally, primarily by associating with the 3' untranslated region (UTR) of their regulatory target mRNAs. Recent work has begun to reveal roles for miRNAs in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Many miRNAs are expressed in cardiac and skeletal muscle, and dysregulated miRNA expression has been correlated with muscle-related disorders. We have previously reported that the expression of muscle-specific miR-1 and miR-133 is induced during skeletal muscle differentiation and miR-1 and miR-133 play central regulatory roles in myoblast proliferation and differentiation in vitro. In this study, we measured the expression of miRNAs in the skeletal muscle of mdx mice, an animal model for human muscular dystrophy. We also generated transgenic mice to overexpress miR-133a in skeletal muscle. We examined the expression of miRNAs in the skeletal muscle of mdx mice. We found that the expression of muscle miRNAs, including miR-1a, miR-133a and miR-206, was up-regulated in the skeletal muscle of mdx mice. In order to further investigate the function of miR-133a in skeletal muscle in vivo, we have created several independent transgenic founder lines. Surprisingly, skeletal muscle development and function appear to be unaffected in miR-133a transgenic mice. Our results indicate that miR-133a is dispensable for the normal development and function of skeletal muscle.
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发表时间: 2007-11-01
期刊: FASEB JOURNAL
影响因子: 4.8
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