Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
J Hum Genet. 2018 Feb;63(2):145-156. doi: 10.1038/s10038-017-0378-7. Epub 2017 Nov 27.
Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.
染色体转移技术，包括染色体修饰，能够将 Mb 大小或多个基因引入所需的细胞或动物中。这项技术使得人类疾病模型和人源化动物的创新发展成为可能，包括唐氏综合征模型鼠和人源化转染色体（Tc）免疫球蛋白鼠。基因组编辑技术发展迅速，允许在各种细胞系和动物中进行基因敲除和敲入等修饰。本综述总结了与染色体转移相关的技术以及染色体转移和基因组编辑的联合技术，主要用于生产人类疾病的细胞/动物模型和人源化动物模型。具体来说，这些包括：（1）利用基因组编辑对中国仓鼠卵巢细胞和小鼠 A9 细胞进行染色体修饰，以高效转移到所需的细胞类型；（2）利用基因组编辑对人源化 Tc 小鼠进行单核苷酸多态性修饰；（3）通过将人类染色体 21 转移到正常人类胚胎干细胞并利用基因组编辑诱导内源性基因的突变，产生与唐氏综合征相关的造血异常疾病模型。这些染色体转移和基因组编辑的组合为药物开发和治疗以及基础研究开辟了新的途径。
