Transgenic animals with inducible, targeted gene expression in brain
Transgenic animals with inducible, targeted gene expression in brain
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DOI：
10.1124/mol.54.3.495
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发表时间：
1998-09-01
影响因子：
3.6
通讯作者：
Nestler, EJ
中科院分区：
文献类型：
--
作者：
Chen, JS;Kelz, MB;Nestler, EJ
近年来，已经在体外开发了几种诱导型基因表达系统，以克服传统转基因小鼠的局限性。其中之一，四环素调节系统，已在体内成功使用。然而，对该系统在体内指导高水平转基因表达以及有效开启和关闭这种表达的能力仍然存在担忧。我们在这里报告了使用在神经元特异性烯醇化酶启动子控制下的改良四环素调节系统产生的几个小鼠品系，这些小鼠将转基因表达引导到特定的大脑区域，包括纹状体、海马小脑CA1区域或大脑新皮质的深层。低剂量的强力霉素（四环素衍生物）可以完全关闭这些小鼠中的转基因表达，并且在不存在强力霉素的情况下将其驱动至非常高的水平。我们证明了三种转基因的组织特异性、诱导性表达：编码荧光素酶（一种报告蛋白）或 Delta FosB 或 cAMP 反应元件结合蛋白 (CREB)（两种转录因子）的转基因。各种转基因小鼠品系展示了一种诱导系统，该系统在特定的大脑区域产生高水平的转基因表达，并代表了研究大脑中这些（或可能的任何其他）基因功能的新颖而强大的工具。
Several inducible gene expression systems have been developed in vitro in recent years to overcome limitations with traditional transgenic mice. One of these, the tetracycline-regulated system, has been used successfully in vivo. Nevertheless, concerns remain about the ability of this system to direct high levels of transgene expression in vivo and to enable such expression to be turned on and off effectively. We report here the generation, using a modified tetracycline-regulated system under the control of the neuron-specific enolase promoter, of several lines of mice that direct transgene expression to specific brain regions, including the striatum, cerebellum CA1 region of the hippocampus, or deep layers of cerebral neocortex. Transgene expression in these mice can be turned off completely with low doses of doxycycline (a tetracycline derivative) and driven to very high levels in the absence of doxycycline. We demonstrate this tissue-specific, inducible expression for three transgenes: those that encode luciferase (a reporter protein) or Delta FosB or the cAMP-response element binding protein (CREB) (two transcription factors). The various lines of transgenic mice demonstrate an inducible system that generates high levels of transgene expression in specific brain regions and represent novel and powerful tools with which to study the functioning of these (or potentially any other) genes in the brain.