Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA USA.
Cell Cycle. 2011 Apr 1;10(7):1059-66. doi: 10.4161/cc.10.7.15233.
The ability to "knockout" specific genes in mice via embryonic stem (ES) cell-based gene-targeting technology has significantly enriched our understanding of gene function in normal and disease phenotypes. Improvements on this original strategy have been developed to enable the manipulation of genomes in a more sophisticated fashion with unprecedented precision. The rat is the model of choice in many areas of scientific investigation despite the lack of rat genetic toolboxes. Most Recent advances of zinc finger nucleases (ZFNs) and rat ES cells are diminishing the gap between rat and mouse with respect to reverse genetic approaches. Importantly, the establishment of rat ES cell-based gene targeting technology, in combination with the unique advantages of using rats, provides new, exciting opportunities to create animal models that mimic human diseases more faithfully. We hereby report our recent results concerning finer genetic modifications in the rat, and propose their potential applications in addressing biological questions.
通过基于胚胎干细胞（ES）细胞的基因靶向技术“敲除”特定基因的能力，极大地丰富了我们对正常和疾病表型中基因功能的理解。对这一原始策略的改进，使我们能够以前所未有的精度更复杂地操纵基因组。尽管缺乏大鼠遗传工具包，但大鼠仍是许多科学研究领域的首选模型。锌指核酸酶（ZFNs）和大鼠 ES 细胞的最新进展正在缩小大鼠和小鼠在反向遗传方法方面的差距。重要的是，基于大鼠 ES 细胞的基因靶向技术的建立，结合使用大鼠的独特优势，为创建更真实地模拟人类疾病的动物模型提供了新的、令人兴奋的机会。我们在此报告我们最近在大鼠中进行更精细的遗传修饰的结果，并提出了它们在解决生物学问题方面的潜在应用。
