Muscle fiber type-predominant promoter activity in lentiviral-mediated transgenic mouse.
Muscle fiber type-predominant promoter activity in lentiviral-mediated transgenic mouse.
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DOI：
10.1371/journal.pone.0016908
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Uchino M
中科院分区：
文献类型：
--
作者：
Suga T;Kimura E;Morioka Y;Ikawa M;Li S;Uchino K;Uchida Y;Yamashita S;Maeda Y;Chamberlain JS;Uchino M
以前注意到基因转导后不同肌纤维类型中基因启动子/增强子活性的变化，但很少分析。小鼠干细胞病毒（MSCV）启动子驱动造血干细胞和其他几种细胞（包括小脑浦肯野细胞）中强大、稳定的基因表达，但尚未在肌肉中进行研究。我们将携带MSCV-EGFP盒的慢病毒载体（LvMSCV-EGFP）注射到胫骨前肌中，并观察到肌纤维、原代培养的成肌细胞和从注射肌肉中分离的肌管中的强EGFP表达。我们还产生了慢病毒介导的转基因小鼠携带MSCV-EGFP盒和检测横纹肌中的转基因表达。LvMSCV-EGFP转基因小鼠表现出纤维类型依赖性的表达变化：I型和IIA型最高，IID/X型居中，IIB型最低。比目鱼肌和膈肌主要由I型和IIA型组成，在肌营养不良症的mdx小鼠模型中受到最严重的影响。对该启动子的进一步分析可能有可能在mdx小鼠严重受累的肌肉中实现某些基因表达。LV介导的转基因小鼠可以证明是一个有用的工具，用于评估各种不同的调节盒的增强子/启动子活性。
Variations in gene promoter/enhancer activity in different muscle fiber types after gene transduction was noticed previously, but poorly analyzed. The murine stem cell virus (MSCV) promoter drives strong, stable gene expression in hematopoietic stem cells and several other cells, including cerebellar Purkinje cells, but it has not been studied in muscle. We injected a lentiviral vector carrying an MSCV-EGFP cassette (LvMSCV-EGFP) into tibialis anterior muscles and observed strong EGFP expression in muscle fibers, primary cultured myoblasts, and myotubes isolated from injected muscles. We also generated lentiviral-mediated transgenic mice carrying the MSCV-EGFP cassette and detected transgene expression in striated muscles. LvMSCV-EGFP transgenic mice showed fiber type-dependent variations in expression: highest in types I and IIA, intermediate in type IID/X, and lowest in type IIB fibers. The soleus and diaphragm muscles, consisting mainly of types I and IIA, are most severely affected in the mdx mouse model of muscular dystrophy. Further analysis of this promoter may have the potential to achieve certain gene expression in severely affected muscles of mdx mice. The Lv-mediated transgenic mouse may prove a useful tool for assessing the enhancer/promoter activities of a variety of different regulatory cassettes.
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