Conditional gene manipulation: Cre-ating a new biological era

Conditional gene manipulation: Cre-ating a new biological era
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DOI:
10.1631/jzus.b1200042
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发表时间:
2012-07
期刊:
Journal of Zhejiang University SCIENCE B
影响因子:
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通讯作者:
Jian Zhang;J. Zhao;Wen-jie Jiang;Xiaoyu Shan;Xiao-Mei Yang;Jian-gang Gao
Jian Zhang;J. Zhao;Wen-jie Jiang;Xiaoyu Shan;Xiao-Mei Yang;Jian-gang Gao
中科院分区:
其他
文献类型:
--
作者:
Jian Zhang;J. Zhao;Wen-jie Jiang;Xiaoyu Shan;Xiao-Mei Yang;Jian-gang Gao

文献摘要

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为了解决常规基因敲除中胚胎致死的问题,位点特异性重组酶(SSR)系统(Cre-loxP、Flp-FRT和ΦC31)已用于组织特异性基因敲除。通过SSR系统和诱导型基因表达系统(四环素和他莫昔芬)的组合,可以实现阶段特异性敲除和转基因表达。这种“SSR+诱导型”条件工具在基因组操作中的应用可以以各种方式扩展。已经开发了条件基因靶向的替代方案,例如条件基因捕获、多用途条件等位基因和条件基因沉默。SSR系统也可用于构建具有点突变和染色体异常的精确疾病模型。有了这些令人兴奋的成就,我们正在迈向一个新时代,在这个时代,整个基因组可以按照我们的意愿进行操纵。
To solve the problem of embryonic lethality in conventional gene knockouts, site-specific recombinase (SSR) systems (Cre-loxP, Flp-FRT, and ΦC31) have been used for tissue-specific gene knockout. With the combination of an SSR system and inducible gene expression systems (tetracycline and tamoxifen), stage-specific knockout and transgenic expression can be achieved. The application of this “SSR+inducible” conditional tool to genomic manipulation can be extended in various ways. Alternatives to conditional gene targeting, such as conditional gene trapping, multipurpose conditional alleles, and conditional gene silencing, have been developed. SSR systems can also be used to construct precise disease models with point mutations and chromosomal abnormalities. With these exciting achievements, we are moving towards a new era in which the whole genome can be manipulated as we wish.