Dhawan J, Rando T A, Elson S L, Bujard H, Blau H M
Department of Neurology, Stanford University School of Medicine, California 94305, USA.
Somat Cell Mol Genet. 1995 Jul;21(4):233-40. doi: 10.1007/BF02255778.
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was suppressed by two orders of magnitude in the presence of tet, and that suppression was reversed when tet was withdrawn.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 genes in vivo, suggesting applications to developmental studies and gene therapy.
对于基因转移的大多数实验和治疗应用而言，调控基因表达的时间和水平比组成型基因表达更为可取。在已开发的用于哺乳动物细胞中药物控制基因表达的系统中，细菌四环素（tet）响应系统具有这样的优势，即它依赖于一种既高度特异又无毒的药物（四环素）。四环素响应系统此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报告基因的表达以及直接注射到心脏中的报告基因的表达。在此我们表明，经口服或肠胃外给药的四环素可调控直接注射到小鼠骨骼肌中的四环素响应质粒的表达。在有四环素存在的情况下，报告基因的表达被抑制了两个数量级，而当去除四环素时，这种抑制作用被逆转。这些数据表明，骨骼肌为体内四环素控制的基因表达提供了一个易于操作且特征明确的靶组织，这为发育研究和基因治疗提供了应用前景。
