Ito Ryoji
Central Institute for Experimental Animals.
Nihon Yakurigaku Zasshi. 2018;151(4):160-165. doi: 10.1254/fpj.151.160.
A humanized mouse, which is efficiently engrafted human cells and tissues, is an important tool to mimic human physiology for biomedical researches. Since 2000s, severe combined immunodeficient mouse strains such as NOG, BRG, and NSG mice have been generated. They are great recipients to create humanized mouse models compared to previous other immunodeficient strains due to their multiple dysfunctions of innate and acquired immunity. Especially, the transfer of human hematopoietic stem cells into these immunodeficient mice has been enabled to reconstitute human immune systems, because the mice show high engraftment level of human leukocyte in peripheral blood (～50%), spleen and bone marrow (60～90%) and generate well-differentiated multilineage human immune cells including lymphoid and myeloid lineage cells. Using these mice, several human disease models such as cancer, allergy, graft-versus-host disease (GVHD), and etc. have been established to understand the pathogenic mechanisms of the diseases and to evaluate the efficacy and safety of novel drugs. In this review, I provide an overview of recent advances in the humanized mouse technology, including generation of novel platforms of genetically modified NOG (next generation NOG) mice and some applications of them to create human disease models for drug discovery in preclinical researches.
一种能高效植入人类细胞和组织的人源化小鼠，是生物医学研究中模拟人类生理学的重要工具。自21世纪以来，已培育出严重联合免疫缺陷小鼠品系，如NOG、BRG和NSG小鼠。与之前的其他免疫缺陷品系相比，由于它们先天性和获得性免疫的多种功能障碍，它们是创建人源化小鼠模型的优秀受体。特别是，将人类造血干细胞移植到这些免疫缺陷小鼠中能够重建人类免疫系统，因为这些小鼠在外周血（约50%）、脾脏和骨髓（60 - 90%）中显示出较高的人类白细胞植入水平，并能产生分化良好的多谱系人类免疫细胞，包括淋巴谱系和髓系谱系细胞。利用这些小鼠，已经建立了几种人类疾病模型，如癌症、过敏、移植物抗宿主病（GVHD）等，以了解疾病的致病机制，并评估新药的疗效和安全性。在这篇综述中，我概述了人源化小鼠技术的最新进展，包括基因编辑NOG（下一代NOG）小鼠新平台的产生以及它们在临床前研究中创建用于药物发现的人类疾病模型的一些应用。
