MYOGENIC VECTOR EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I STIMULATES MUSCLE-CELL DIFFERENTIATION AND MYOFIBER HYPERTROPHY IN TRANSGENIC MICE
MYOGENIC VECTOR EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I STIMULATES MUSCLE-CELL DIFFERENTIATION AND MYOFIBER HYPERTROPHY IN TRANSGENIC MICE
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DOI：
10.1074/jbc.270.20.12109
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发表时间：
1995-05-19
影响因子：
4.8
通讯作者：
SCHWARTZ, RJ
中科院分区：
文献类型：
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作者：
COLEMAN, ME;DEMAYO, F;SCHWARTZ, RJ
将禽类骨骼α-肌动蛋白基因用作用于构建肌原性表达载体的模板，所述肌原性表达载体用于在培养的肌细胞和转基因小鼠的横纹肌中指导人IGF-I cDNA的表达。禽骨骼肌α-肌动蛋白基因的近端启动子区与第一个内含子和3 '端非编码侧翼序列的1.8个内切酶一起指导人胰岛素样生长因子I（IGF-I）在稳定转染的C2 C12成肌细胞和转基因小鼠中的高水平表达。肌动蛋白/IGF-1杂合基因在C2 C12肌细胞中的表达增加了肌源性碱性螺旋-环-螺旋因子和收缩蛋白mRNA的水平，并增强了肌管形成。肌动蛋白/IGF-1杂合基因在小鼠中的表达使骨骼肌中的IGF-1浓度升高47倍，导致肌纤维肥大，血清和体重中的IGF-1浓度没有因转基因表达而增加，表明转基因表达的作用是局部的。这些结果表明骨骼肌中IGF-I的持续过表达导致肌纤维肥大，并为利用基于骨骼α-肌动蛋白的载体操纵肌肉生理学提供了基础。
The avian skeletal alpha-actin gene was used as a template for construction of a myogenic expression vector that was utilized to direct expression of a human IGF-I cDNA in cultured muscle cells and in striated muscle of transgenic mice. The proximal promoter region, together with the first intron and 1.8 kilobases of 3'-noncoding flanking sequence of the avian skeletal alpha-actin gene directed high level expression of human insulin-like growth factor I (IGF-I) in stably transfected C2C12 myoblasts and transgenic mice. Expression of the actin/IGF-I hybrid gene in C2C12 muscle cells increased levels of myogenic basic helix-loop-helix factor and contractile protein mRNAs and enhanced myotube formation, Expression of the actin/IGF-I hybrid gene in mice elevated IGF-I concentrations in skeletal muscle 47-fold resulting in myofiber hypertrophy, IGF-I concentrations in serum and body weight were not increased by transgene expression, suggesting that the effects of transgene expression were localized, These results indicate that sustained overexpression of IGF-I in skeletal muscle elicits myofiber hypertrophy and provides the basis for manipulation of muscle physiology utilizing skeletal alpha-actin-based vectors.