Genome Editing Research and Development Center, Graduate School of Medicine, Osaka University, Osaka, Japan.
Institute of Experimental Animal Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
J Hum Genet. 2018 Feb;63(2):115-123. doi: 10.1038/s10038-017-0346-2. Epub 2017 Nov 20.
Laboratory rats and mice are representative experimental animals for models of human disease. The emergence of genome editing technologies has enabled us to produce a variety of genetically modified animals, including rats, as a means of elucidating the in vivo functions of the gene of interest and characterizing the molecular mechanisms of human disease. Several advanced techniques for knock-in methodologies in rats are currently in development, which permit researchers to introduce precise nucleotide modifications at target sites in the rat's genome. Furthermore, recent studies with knock-out rats have revealed that observed disease phenotypes are often more similar than mouse models to those of humans. In this article, we introduce the methodologies for efficient gene manipulation in rats using genome editing technologies, and describe the advances made using rats for human disease models. We also discuss the importance of gene manipulation in animal models for the better understanding of fundamental processes among different species.
实验大鼠和小鼠是人类疾病模型的代表性实验动物。基因组编辑技术的出现使我们能够生产各种基因修饰动物，包括大鼠，以此来阐明感兴趣基因的体内功能，并阐明人类疾病的分子机制。目前正在开发几种大鼠基因敲入方法的先进技术，这些技术可使研究人员在大鼠基因组的靶位点引入精确的核苷酸修饰。此外，最近使用基因敲除大鼠的研究表明，观察到的疾病表型通常比小鼠模型更类似于人类。在本文中，我们介绍了使用基因组编辑技术在大鼠中进行有效基因操作的方法，并描述了使用大鼠作为人类疾病模型所取得的进展。我们还讨论了在不同物种之间更好地理解基本过程的动物模型中进行基因操作的重要性。
