School of Life Science, Shandong University, Jinan, China.
J Zhejiang Univ Sci B. 2012 Jul;13(7):511-24. doi: 10.1631/jzus.B1200042.
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.
为了解决传统基因敲除中胚胎致死的问题,已经使用了位点特异性重组酶(SSR)系统(Cre-loxP、Flp-FRT 和 ΦC31)进行组织特异性基因敲除。通过将 SSR 系统与诱导性基因表达系统(四环素和他莫昔芬)相结合,可以实现特定阶段的基因敲除和转基因表达。这种“SSR+诱导”条件性工具在基因组操作中的应用可以以各种方式扩展。已经开发了替代条件性基因靶向的方法,例如条件性基因捕获、多用途条件性等位基因和条件性基因沉默。SSR 系统还可用于构建具有点突变和染色体异常的精确疾病模型。随着这些令人兴奋的成就,我们正在迈向一个新的时代,可以随心所欲地对整个基因组进行操作。