Gene induction in mature oligodendrocytes with a PLP-tTA mouse line
Gene induction in mature oligodendrocytes with a PLP-tTA mouse line
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DOI：
10.1002/dvg.20808
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发表时间：
2012-05-01
期刊：
影响因子：
1.5
通讯作者：
Ikenaka, Kazuhiro
中科院分区：
文献类型：
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作者：
Inamura, Naoko;Sugio, Shouta;Ikenaka, Kazuhiro
成熟的少突胶质细胞对髓鞘的维持至关重要。为了理解这一点的分子基础，需要对成熟的少突胶质细胞进行遗传操作。在这里，我们产生了一个成熟的少突胶质细胞tTA（四环素控制的转录激活因子）的小鼠系，与tTA依赖性启动子驱动所需的转基因的表达，可用于获得功能的研究。我们使用了少突胶质细胞启动子，小鼠蛋白脂质蛋白（PLP）启动子，表达tTA，并产生了PLP-mtTA小鼠系。在成人中，mtTA mRNA主要在脑白色物质中检测到，它与PLP mRNA共定位。通过与具有tTA依赖性启动子驱动黄色荧光蛋白表达的小鼠（tetO-YFP小鼠）杂交来证实mtTA介导的基因诱导。PLP-mtTA：：tetO-YFP小鼠中的YFP诱导与成年成熟少突胶质细胞和髓鞘形成前阶段髓鞘形成少突胶质细胞中的PLP表达一致。该PLP-mtTA小鼠系是第一个能够用泰特系统在成熟少突胶质细胞中进行功能获得研究的小鼠系。Genesis 50：424428，2012. (C)2011 Wiley Periodicals，Inc.
Mature oligodendrocytes are critical for myelin maintenance. To understand the molecular basis for this, genetic manipulation of mature oligodendrocytes is needed. Here we generated a mature oligodendrocyte tTA (tetracycline-controlled transcriptional activator) mouse line which, in combination with a tTA-dependent promoter line driving the expression of the desired transgene, can be used for gain-of-function studies. We used an oligodendrocyte promoter, the mouse proteolipid protein (PLP) promoter, to express mammalianized tTA, and generated a PLP-mtTA mouse line. In adults, mtTA mRNA was predominantly detected in brain white matter where it co-localized with PLP mRNA. mtTA-mediated gene induction was confirmed by crossing to mice with a tTA-dependent promoter driving expression of yellow fluorescent protein (tetO-YFP mice). YFP induction in PLP-mtTA::tetO-YFP mice was consistent with PLP expression in adult mature oligodendrocytes and premyelinating-stage myelinating oligodendrocytes. This PLP-mtTA mouse line is the first to enable gain-of-function studies in mature oligodendrocytes with the tet system. genesis 50:424428, 2012. (C) 2011 Wiley Periodicals, Inc.