Tetracycline-controlled transcriptional regulation systems: countermeasures to eliminate basal transgene leaks in Tet-based systems  

作　　者：XIAO Dong SUN Yan GU Weiwang CHEN Xigu 

机构地区：[1]Center of Experimental Animals and Institute of Comparative Medicine, Southern Medical University, Guangzhou 510515, China [2]Center of Experimental Animals, Sun Yat-sen University, Guangzhou 510080, China

出　　处：《Progress in Natural Science:Materials International》2007年第1期11-19,共9页自然科学进展·国际材料（英文版）

基　　金：Supported by National Natural Science Foundation of China(Grant Nos.30271177 and 39870676);National 9th Five-Year Plan Program(Grant No.101033);Major Science and Technology Projects of Guangdong Province(Grant Nos.B602 and 2003C60101);Natural Science Foundation of Gdoctoral Fellowship Foundation of China(Series 29)

摘　　要：To analyze the function of any given transgene（s） accurately in transgenic mice, and to produce credible transgenic animal models of various human diseases （precisely and realistically mimicking disease states）, it is critical to be able to control gene expression in the animals conditionally. The ability to switch gene expression ＂on＂ or ＂off＂ in the restricted cells or tissue（s） at specific time（s） allows unprecedented flexibility for exploring gene function（s） in both the health and the disease. Pioneering work on inducible transgene expression has led to the development of a wide variety of controlled gene expression systems that meet this criterion. Among them, the tetracycline-inducible systems （e. g. Tet-off and Tet-on） have been widely, frequently and successfully employed in vitro and in vivo. These systems, however, are not always tight but leaky; sometimes the leakage is significant. In some circumstances, the resulting leak is acceptable, but in others, it is more problematic. Though these systems face this disadvantage, i.e. basal transgene leakage in vitro and in vivo, several approaches, including using improved versions （e. g. rtTA2^S-M2 and rtTA2^S-S2） of rtTA, tetracycline-controlled transcriptional silencer （tTS）, an ＂ideal＂ minimal promoter in responsive components or combinations thereof, have been developed to avoid this limitation effectively. In this review we discuss the countermeasures available to eliminate basal transgene leakage from Tet-based systems.为了在转基因的鼠标精确地分析任何给定的 fransgene 的函数，并且生产，可信的转基因的动物各种各样的人的疾病当模特儿(精确并且写实地模仿国王疾病状态) ，有条件地对在动物的 contiol 基因表示有能力是批评的。在特定的时间在限制房间或纸巾“上”或“离开”交换基因表示的能力为处于健康和疾病探索基因功能允许 Lnprecedented 灵活性。在可诱导的 transgene 表示上开创工作导致了满足这个标准的控制基因表达式系统的一个 de 变化的开发。在他们之中，四圜素可诱导的系统(例如 Tet 离开并且在 Tet 上) dely，经常并且成功地在 vitro 并且在 vivo 被采用了。然而，这些系统不总是紧张却漏；有时漏是重要的。在一些情形，产生漏缝是可接受的，但是在其它，它是更有问题的。不过，这些系统面对这劣势，我。e。在 vitro 并且在 vivo 的基础 transgene 漏，几条途径，用改进版本包括(例如 rtTA2 <SUP > S </SUP>-M2 和 rtTA2 <SUP > rtTA 的 s </SUP>-S2)，控制四圜素的 transcriptional silencer ( tTS )，在应答的部件或它的联合的一个理想的最小的倡导者，被开发了有效地避免这限制。在这评论，我们讨论可得到的 counteimeasures 消除基础 transgene 漏 frcrn 基于 Tet 的系统。

关 键 词：tetracycline inducible system transgenic mice leaky expression transcriptional silencer 

分 类 号：S511[农业科学—作物学] S188