University of Colorado, School of Medicine, Anschutz Medical Campus, Department of Pediatrics, Section of Developmental Biology, 12801 E 17th Avenue, Aurora, CO 80045, USA.
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Development. 2023 Apr 15;150(8). doi: 10.1242/dev.201531. Epub 2023 Apr 19.
Transgenesis is an essential technique for any genetic model. Tol2-based transgenesis paired with Gateway-compatible vector collections has transformed zebrafish transgenesis with an accessible modular system. Here, we establish several next-generation transgenesis tools for zebrafish and other species to expand and enhance transgenic applications. To facilitate gene regulatory element testing, we generated Gateway middle entry vectors harboring the small mouse beta-globin minimal promoter coupled to several fluorophores, CreERT2 and Gal4. To extend the color spectrum for transgenic applications, we established middle entry vectors encoding the bright, blue-fluorescent protein mCerulean and mApple as an alternative red fluorophore. We present a series of p2A peptide-based 3' vectors with different fluorophores and subcellular localizations to co-label cells expressing proteins of interest. Finally, we established Tol2 destination vectors carrying the zebrafish exorh promoter driving different fluorophores as a pineal gland-specific transgenesis marker that is active before hatching and through adulthood. exorh-based reporters and transgenesis markers also drive specific pineal gland expression in the eye-less cavefish (Astyanax). Together, our vectors provide versatile reagents for transgenesis applications in zebrafish, cavefish and other models.
转基因技术是任何遗传模型的重要技术。基于 Tol2 的转基因技术与兼容 Gateway 的载体集合相结合,通过可访问的模块化系统改变了斑马鱼的转基因技术。在这里,我们为斑马鱼和其他物种建立了几种下一代转基因工具,以扩展和增强转基因应用。为了方便基因调控元件的测试,我们生成了携带小鼠β珠蛋白最小启动子的 Gateway 中间入口载体,该启动子与几种荧光蛋白、CreERT2 和 Gal4 偶联。为了扩展转基因应用的光谱,我们建立了中间入口载体,编码明亮的蓝色荧光蛋白 mCerulean 和 mApple,作为替代红色荧光蛋白。我们提出了一系列基于 p2A 肽的 3' 载体,带有不同的荧光蛋白和亚细胞定位,用于共同标记表达感兴趣蛋白的细胞。最后,我们建立了携带斑马鱼 exorh 启动子的 Tol2 目的载体,该启动子驱动不同的荧光蛋白作为松果腺特异性转基因标记物,在孵化前和成年期都具有活性。基于 exorh 的报告基因和转基因标记物也在无眼洞穴鱼(Astyanax)中驱动特定的松果腺表达。总之,我们的载体为斑马鱼、洞穴鱼和其他模型中的转基因应用提供了多功能试剂。