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山东大学学报(理学版) ›› 2011, Vol. 46 ›› Issue (10): 183-196.

• 论文 • 上一篇    下一篇

小鼠基因敲除的研究进展

张剑,杨晓梅*,高建刚*   

  1. 山东大学生命科学学院, 山东 济南 250100
  • 收稿日期:2011-07-15 出版日期:2011-10-20 发布日期:2011-10-18
  • 通讯作者: 高建刚(1963- ),男,博士,教授,博士生导师,主要研究方向为干细胞生物学. Email: jggao@sdu.edu.cn
  • 作者简介:张剑(19- ),男,博士,主要研究方向为Email: zhj8226@sdu.edu.cn

Advances of gene knockout in mice

ZHANG Jian, YANG Xiao-mei*, GAO Jian-gang*   

  1. School of Life Science, Shandong University, Jinan 250100, Shandong, China
  • Received:2011-07-15 Online:2011-10-20 Published:2011-10-18

摘要:

随着人类基因组计划(HGP)的顺利完成,后基因时代的生物学研究迫切需要一种有效的基因功能分析方法。基因敲除小鼠模型的应用,为研究基因的功能和寻找新的治疗人类疾病的干预措施提供了有力支持。基因打靶和基因捕获是两种不同的通过胚胎干细胞(ES细胞)制作基因敲除小鼠的技术。基因捕获具有高通量、随机性、序列标记等特点,而基因打靶则是针对特定基因的敲除。自基因打靶和基因捕获小鼠首次亮相距今已有近20年的时间。近年来,针对基因打靶和基因捕获的新工具不断涌现,并且相应的组织也已经成立。这些组织能够利用这两种方法敲除小鼠基因组中的基因。国际基因捕获协会(The International Gene Trap Consortium,IGTC)和基因敲除小鼠计划(The Knockout Mouse Project,KOMP)已着手创建世界范围内用于科研的便利资源,并且计划敲除所有小鼠的基因。KOMP的组织者认为这与HGP一样具有重要意义。从传统的基因打靶到现在的高通量的条件基因打靶,基因打靶的方法已经发生了很大的变化。捕获和打靶两者的组合优势大大提升了基因捕获的范围和基因打靶的效率。作为一种新开发的插入式突变系统,转座子在捕获基因方面比逆转录病毒更具有优势。国际基因敲除小鼠协会(The International Knockout Mouse Consortium,IKMC)的出现标志着全球性合作的开始。该组织致力于系统地敲除小鼠基因组中所有基因,进而开展功能基因组的研究。

关键词: 基因打靶, 基因捕获, 转座子, 胚胎干细胞, 基因敲除小鼠

Abstract:

With the successful completion of Human Genome Project (HGP),the biological research of postgenome era has a urgent need for an effective gene function analysis. Application of knockout mouse model provides a strong support for the study of gene function and the search for new therapeutic interventions in human disease. As two different techniques, gene targeting and gene trapping are producing knockout mice from embryonic stem cells (ES cells).The characteristic of gene trapping is highthroughput, random, and sequence tagged,while gene targeting is a specific gene knockout. Two decades ago, the first gene targeting and gene trapping mice were generated. In recent years, new tools for gene targeting and gene trapping are emerging, and the related organizations have been formed. These organizations can knock out genes in the mouse genome using these two methods. The international gene trap consortium (IGTC) and the knockout mouse project (KOMP) have begun to create a worldwide resource for research facilities, and plan to knock out all the mouse genes. KOMP organizers consider it as important as the HGP. From conventional gene targeting to high throughput conditional gene targeting, gene targeting methods have changed. The combined advantages of trapping and targeting enhance the gene trapping spectrum and gene targeting efficiency. As a newly developed insertional mutation system, transposons in trapping genes have more advantages than retrovirus. Emergence of the international knockout mouse consortium (IKMC) is the beginning of global cooperation. The organization is committed to systematically knock out all genes in the mouse genome, and then to carry out functional genomics studies.

Key words: gene targeting, gene trapping, transposon, ES cells, knockout mouse

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