ES-mouse/Virus Core, International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Laboratory for Mouse Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Curr Opin Biotechnol. 2019 Aug;58:137-145. doi: 10.1016/j.copbio.2019.03.003. Epub 2019 Apr 5.
Systems-biological approaches, such as comprehensive identification and analysis of system components and networks, are necessary to understand design principles of human physiology and pathology. Although reverse genetics using mouse models have been used previously, it is a low throughput method because of the need for repetitive crossing to produce mice having all cells of the body with knock-out or knock-in mutations. Moreover, there are often issues from the interspecific gap between humans and mice. To overcome these problems, high-throughput methods for producing knock-out or knock-in mice are necessary. In this review, we describe 'next-generation' human genetics, which can be defined as high-throughput mammalian genetics without crossing to knock out human-mouse ortholog genes or to knock in genetically humanized mutations.
系统生物学方法，例如全面鉴定和分析系统成分和网络，对于理解人类生理学和病理学的设计原理是必要的。尽管以前使用了基于小鼠模型的反向遗传学，但由于需要重复杂交才能产生具有敲除或敲入突变的所有体细胞的小鼠，所以这是一种低通量方法。此外，通常还存在人与小鼠之间种间差异的问题。为了克服这些问题，需要高通量的方法来生产敲除或敲入小鼠。在这篇综述中，我们描述了“下一代”人类遗传学，它可以定义为没有杂交的高通量哺乳动物遗传学，可以敲除人鼠同源基因或敲入基因人源化突变。
