背景:传统基因敲除技术不能在特定时间敲除目标基因,动物模型往往在胚胎发育时期或出生后死亡,限制了基因功能的研究。目的:综述时间特异性基因敲除技术的研究现状。方法:以“gene knockout,inducer,Cre/loxP system”为关键词检索建库至2014年8月 PubMed 数据库。从初检文献中排除重复实验和与研究目的无关的文献,通过分析结果对时间特异性基因敲除技术的研究做出总结。结果与结论:大多数个体全部细胞基因敲除动物在出生后往往不能存活,它们因为某个重要基因缺失后胚胎早期产生严重生理性缺陷而死亡。因此,对于某个基因在特定时间的功能、生物个体在特定发育时间段内的遗传特征、以及某些获得性疾病在特定时间内的治疗等一系列问题,由于研究方法的局限性至今进展有限。而条件性基因敲除动物,尤其是时间特异性基因敲除动物的出现为这些领域的研究提供了研究模型。文章总结了近几年国内外关于时间特异性基因敲除动物的研究、发展及其应用,阐明特定基因的时间特异性基因敲除技术在科学研究领域的重大意义和广阔前景。
BACKGROUND: The target gene cannot be deleted at specific time by using conditional gene knockout system. Most gene knockout animals cannot survive during embryonic development and after birth, which limits the study of gene function. OBJECTIVE: To review the recent advances about time-specific gene knockout technology. METHODS: An online search in PubMed was performed from the initial stage of database establishment to August 2014. The key words were gene knockout, inducer and Cre/loxP system. The repeated experiment and unrelated articles were excluded during primary search. A summary was made by analyzing time-specific gene knockout technology. RESULTS AND CONCLUTION: Most important gene knockout animals could not survive after birth, or die at early embryonic stage due to serious physical defects induced by an important gene deletion. Therefore, the progress in the functionality of a gene at a particular time, the genetic characteristics of an individual organism in a particular developmental period, and the treatment of certain acquired disease at a given time have been limited because of the limitations of research methods. However, the occurrence of conditional gene knockout animals, especial y time-specific knockout animals, provides a research model for the study of these areas. This study reviewed the recent advances, development and application about time-specific gene knockout animals, and discussed the significance and broad prospects of time-specific gene knockout technology of specific genes in the field of scientific research.