基因修饰中国猕猴技术的研究进展  

Advances in Genetically Modified Chinese Macaques

作　　者：马云瀚[1,2,3] 杨世华[2,3] 

机构地区：[1]昆明理工大学医学院,昆明650500 [2]华南农业大学兽医学院,广州510642 [3]广东省兽医临床重大疾病综合防控实验室,广州510642

出　　处：《生物化学与生物物理进展》2014年第11期1089-1098,共10页Progress In Biochemistry and Biophysics

基　　金：科技部重大科学研究计划重大科学问题导向项目(2012CBA01302);新世纪国家优秀人才支持计划项目(NCET-12-1078);国家自然科学基金资助项目(31071279);广东省教育厅科技创新项目(2013KJCX0029)~~

摘　　要：实验动物是人类疾病研究的终身伴侣.由于在遗传进化、生理生化及病理方面与人类接近,猕猴成为不可或缺的实验动物.基因修饰猕猴(或称基因工程猕猴)是从基因和基因调控角度在机体整体发育水平上认识人类生理和病理分子机制的重要实验材料和高等模型动物.目前,高效的猕猴辅助生殖技术(assisted reproductive technologies,ARTs)和精确的基因编辑技术成为研制基因修饰猕猴的唯一途径.在中国猕猴(或恒河猴)的ARTs方面,已经完成了精液采集与冷冻保存、超数排卵、体外受精和胚胎培养、胚胎移植和妊娠管理,高效完成了"试管猴".在基因编辑技术方面,最近创建了ZFN(zinc-finger nucleases)、TALEN(transcription activator-like effector nucleases)、CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/Cas9)载体,为制作基因修饰猕猴创造了条件.我国已经成功研制了转基因和基因敲除的中国猕猴.随着基因编辑技术的突破和发展,结合我国现有丰富的实验猕猴资源,研究避免猕猴的生殖生理障碍,我国有望成为国际化的、重要的基因修饰猕猴研发和生产基地.Experimental animals and human disease research are a symbiotic relationship in life science field. Due to the proximity with humans in the aspects of genetic evolution, physiology, biochemistry and pathology, macaque monkeys become indispensable experimental animals in biomedicine research. Genetically modified macaques（also known as genetic engineering macaques） could be important experimental materials and advanced animal models for understanding molecular mechanisms of human physiology and pathology under observation of expression and being regulation of the targeted gene modified in the whole life of animals. Currently, combination of high-efficient assisted reproductive technologies（ARTs） in macaques with precise gene editing technologies is the only way of developing genetically modified monkeys. Now in China, ARTs in Chinese rhesus macaques included semen collection and cryopreservation, superovulation, in vitro fertilization and embryo culture, embryo transfer and pregnancy management, thus ＂test-tube monkey＂, and all have been efficiently completed. The establishment and development of the current gene editing technology, ZFN（zinc-finger nucleases）, TALEN（transcription activator-like effector nucleases） and CRISPR/Cas9（Clustered regularly interspaced short palindromic repeats/Cas9）, create great chances for production of genetically modified macaques. Scientists in China have successfully developed transgenic macaques with overexpression of green fluorescence protein gene and gene mutagenesis in macaques. With the breakthrough and development of various technologies, combined with abundant experimental macaque resources, avoiding various reproductive physiological obstructions of macaques, China is expected to become an appropriate international base in application of genetic engineering macaques.

关 键 词：中国猕猴 ARTS 基因编辑技术 基因工程动物 

分 类 号：Q492[生物学—生理学] Q812