Tetracycline-regulated gene expression following direct gene transfer into mouse skeletal muscle

Tetracycline-regulated gene expression following direct gene transfer into mouse skeletal muscle
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直接基因转移至小鼠骨骼肌后四环素调节的基因表达

DOI:
10.1007/bf02255778
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发表时间:
1995
期刊:
Somatic Cell and Molecular Genetics
影响因子:
--
通讯作者:
H. Blau
H. Blau
中科院分区:
--
文献类型:
--
作者:
J. Dhawan;T. Rando;S. Elson;H. Bujard;H. Blau

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对于基因转移的大多数实验和治疗应用,基因表达的时间和水平的调节优选于组成型基因表达。在已经开发的用于哺乳动物细胞中四环素控制的基因表达的系统中,细菌四环素(泰特)响应系统具有依赖于高度特异性和无毒的药物(泰特)的优点。tet应答系统先前已被用于调节培养细胞中细胞周期调节蛋白的表达,植物和转基因小鼠中的报告基因以及直接注射到心脏中的报告基因。在这里,我们表明,口服或胃肠外给予泰特调节tet反应质粒直接注射到小鼠骨骼肌的表达。报告基因的表达被抑制了两个数量级的泰特的存在下,这种抑制被逆转时,泰特撤回。这些数据表明,骨骼肌提供了一个可访问的和良好的特点tet控制的基因表达的体内靶组织,建议应用发育研究和基因治疗。
For most experimental and therapeutic applications of gene transfer, regulation of the timing and level of gene expression is preferable to constitutive gene expression. Among the systems that have been developed for pharmacologically controlled gene expression in mammalian cells, the bacterial tetracycline (tet)-responsive system has the advantage that it is dependent on a drug (tet) that is both highly specific and non-toxic. The tet-responsive system has been previously used to modulate expression of cell cycle regulatory proteins in cultured cells, reporter genes in plants and transgenic mice and reporter genes directly injected into the heart. Here we show that orally or parenterally administered tet regulates expression of tet-responsive plasmids injected directly into mouse skeletal muscle. Reporter gene expression was suppressed by two orders of magnitude in the presence of tet, and that suppression was reversed when tet was withdrawn. These data show that skeletal muscle offers an accessible and well characterized target tissue for tet-controlled expression of genesin vivo, suggesting applications to developmental studies and gene therapy.
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