Whole-rat conditional gene knockout via genome editing
Whole-rat conditional gene knockout via genome editing
复制标题
DOI：
10.1038/nmeth.2516
复制
发表时间：
2013-07-01
期刊：
影响因子：
48
通讯作者：
Cui, Xiaoxia
中科院分区：
文献类型：
--
作者：
Brown, Andrew J.;Fisher, Daniel A.;Cui, Xiaoxia
在时间和/或空间控制下具有基因修饰的动物模型对功能基因组学和医学研究具有极其重要的价值。在此我们报道了通过将锌指核酸酶（ZFNFNs）显微注射到受精卵中产生组织特异性基因敲除大鼠的研究。我们培育出了带有loxP侧翼（可诱导型）等位基因以及一个由酪氨酸羟化酶启动子驱动的cre等位基因的大鼠，并在体内证明了Cre依赖性基因破坏。我们的数据表明，原核显微注射ZFNs是一种高效且快速的创建条件性基因敲除大鼠的方法，它也应该适用于其他物种。
Animal models with genetic modifications under temporal and/or spatial control are invaluable to functional genomics and medical research. Here we report the generation of tissue-specific knockout rats via microinjection of zinc-finger nucleases (ZFNFNs) into fertilized eggs. We generated rats with loxP-flanked (floxed) alleles and a tyrosine hydroxylase promoter-driven cre allele and demonstrated Cre-dependent gene disruption in vivo. Pronuclear microinjection of ZFNs, shown by our data to be an efficient and rapid method for creating conditional knockout rats, should also be applicable in other species.