Allen Institute for Brain Science, Seattle, WA 98109, USA.
Departments of Neurobiology and Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2018 Jul 12;174(2):465-480.e22. doi: 10.1016/j.cell.2018.06.035.
Modern genetic approaches are powerful in providing access to diverse cell types in the brain and facilitating the study of their function. Here, we report a large set of driver and reporter transgenic mouse lines, including 23 new driver lines targeting a variety of cortical and subcortical cell populations and 26 new reporter lines expressing an array of molecular tools. In particular, we describe the TIGRE2.0 transgenic platform and introduce Cre-dependent reporter lines that enable optical physiology, optogenetics, and sparse labeling of genetically defined cell populations. TIGRE2.0 reporters broke the barrier in transgene expression level of single-copy targeted-insertion transgenesis in a wide range of neuronal types, along with additional advantage of a simplified breeding strategy compared to our first-generation TIGRE lines. These novel transgenic lines greatly expand the repertoire of high-precision genetic tools available to effectively identify, monitor, and manipulate distinct cell types in the mouse brain.
现代遗传方法在获取大脑中不同类型的细胞并研究其功能方面具有强大的作用。在这里，我们报告了一系列大型的驱动和报告基因转基因小鼠品系，包括 23 种新的针对各种皮层和皮层下细胞群的驱动基因，以及 26 种新的表达一系列分子工具的报告基因。特别是，我们描述了 TIGRE2.0 转基因平台，并介绍了依赖 Cre 的报告基因，这些报告基因可实现光生理、光遗传学和遗传定义的细胞群的稀疏标记。与我们的第一代 TIGRE 线相比，TIGRE2.0 报告基因突破了单拷贝靶向插入转基因在广泛的神经元类型中转基因表达水平的障碍，同时还具有简化的繁殖策略的优势。这些新型转基因线极大地扩展了可用的高精度遗传工具的范围，可有效识别、监测和操作小鼠大脑中的不同细胞类型。
