Imayoshi Itaru, Ohtsuka Toshiyuki, Metzger Daniel, Chambon Pierre, Kageyama Ryoichiro
Institute for Virus Research, Kyoto University, Kyoto, Japan.
Genesis. 2006 May;44(5):233-8. doi: 10.1002/dvg.20212.
Neural stem cells are known to give rise to distinct subtypes of neurons and glial cells over time by changing their competency. However, precise characterization of neural stem cells at various developmental stages remains to be performed. For such analysis, a tool to manipulate neural stem cells at different time points is necessary. Here, we generated transgenic mice that express Cre-ER(T2) in the ventricular zone of the developing nervous system under the control of the nestin promoter and enhancer (Nes-CreER(T2)). In mice expressing Cre-ER(T2) at appropriate levels, Cre recombinase activity was mostly inactive but efficiently activated by tamoxifen within 1 day. When such mice were crossed with the ROSA-26 or Z/EG reporter mice, neural stem cells were permanently labeled after administration of tamoxifen. Thus, Nes-CreER(T2) mice offer a powerful tool to manipulate neural stem cells genetically at desired time points.
众所周知，神经干细胞会随着时间推移通过改变其能力产生不同类型的神经元和胶质细胞亚型。然而，对处于不同发育阶段的神经干细胞进行精确表征仍有待开展。对于此类分析，需要一种在不同时间点操纵神经干细胞的工具。在此，我们构建了转基因小鼠，其在巢蛋白启动子和增强子（Nes-CreER(T2)）的控制下，在发育中的神经系统的脑室区表达Cre-ER(T2)。在以适当水平表达Cre-ER(T2)的小鼠中，Cre重组酶活性大多处于无活性状态，但在1天内可被他莫昔芬有效激活。当此类小鼠与ROSA-26或Z/EG报告基因小鼠杂交时，给予他莫昔芬后神经干细胞会被永久标记。因此，Nes-CreER(T2)小鼠提供了一种在所需时间点对神经干细胞进行基因操纵的强大工具。
