Transgenic mice for conditional gene manipulation in astroglial cells
Transgenic mice for conditional gene manipulation in astroglial cells
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DOI：
10.1002/glia.20570
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发表时间：
2007-11-15
期刊：
影响因子：
6.2
通讯作者：
Pfrieger, Frank W.
中科院分区：
文献类型：
--
作者：
Slezak, Michal;Goritz, Christian;Pfrieger, Frank W.
星形胶质细胞被认为在大脑中发挥多种功能，但由于缺乏操纵这些细胞的工具，很难在体内证明这一点。在这里，我们报告了新的转基因小鼠品系，允许条件基因消融星形胶质细胞使用他莫昔芬-（TAM-）诱导的CreER（T2）/loxp系统和细菌人工染色体（BAC）为基础的转基因。在成年转基因小鼠中，CreER（T2）表达由钠依赖性谷氨酸/天冬氨酸转运蛋白（Glast/Slc 1a 3）或连接蛋白30（Cx 30/Gjb 6）的启动子驱动，腹腔内注射TAM诱导整个大脑星形胶质细胞中Cre介导的重组。如基于酶的报告细胞系和免疫组织化学染色所示，靶向功效以区域特异性方式从20%至90%变化。此外，Glast-系允许靶向视网膜Muller细胞和成人大脑神经源性区域中的成人神经干细胞/祖细胞。在载脂蛋白a（ApoE）或水通道蛋白4（Aqp 4）启动子的控制下表达CreER（T2）的转基因小鼠在中枢神经系统（CNS）的不同区域显示出诱导性重组，尽管水平较低。转基因株系在特定的外周器官中表现出TAM诱导的重组。这些新的小鼠品系应该有助于进一步探索星形胶质细胞与脑功能的相关性，以及它们对衰老、疾病或损伤引起的病理状态的贡献。(C)2007 Wiley-Liss，Inc.
Astrocytes are thought to exert diverse functions in the brain, but it has been difficult to prove this in vivo because of a scarcity of tools to manipulate these cells. Here, we report the generation of new transgenic mouse lines that allow for conditional gene ablation in astrocytes using the tamoxifen- (TAM-) inducible CreER(T2)/loxp system and bacterial artificial chromosome (BAC)-based transgenesis. In adult transgenic mice, where CreER(T2) expression is driven by the promoter of the sodium-dependent glutamate/aspartate transporter (Glast/Slc1a3) or of connexin 30 (Cx30/Gjb6), intraperitoneal TAM-injection induced Cre-mediated recombination in astroglial cells throughout the brain. Targeting efficacies varied in a region-specific manner from 20 to 90% as indicated by enzyme-based reporter lines and immunohistochemical staining. In addition, the Glast-line allowed to target retinal Muller cells and adult neural stem/progenitor cells in neurogenic regions of the adult brain. Transgenic mice expressing CreER(T2) under the control of the apolipoprotein a (ApoE) or aquaporin 4 (Aqp4) promoter showed inducible recombination in different areas of the central nervous system (CNS) albeit at low levels. Transgenic lines showed TAM-induced recombination in specific peripheral organs. These new mouse lines should help to further explore the relevance of astrocytes for brain function, as well as their contribution to pathological conditions because of aging, disease or injury. (C) 2007 Wiley-Liss, Inc.