Appearances can be deceiving: phenotypes of knockout mice
Appearances can be deceiving: phenotypes of knockout mice
复制标题
DOI：
10.1093/bfgp/elm008
复制
发表时间：
2007-06-01
期刊：
影响因子：
--
通讯作者：
Dear, T. Neil
中科院分区：
文献类型：
--
作者：
Barbaric, Ivana;Miller, Gaynor;Dear, T. Neil
在哺乳动物功能基因组学领域，后基因组时代的主要目标之一是阐明基因组中所有基因的功能。胚胎干细胞中强大的基因靶向技术使得能够简单地产生缺乏特定基因的小鼠。然而，很明显，在一部分这样的基因敲除小鼠中，没有检测到表型的偏差。小鼠表型分析领域的进展和对每个基因敲除的广泛表型分析测试的使用表明，异常表型有时会在最初未预料到的生理区域中检测到，或仅在某些条件下表现出来，强调了仔细表型研究的必要性。然而，一些基因的作用只有在另一个基因失活时才变得明显，这表明了生物鲁棒性的现象。与酵母不同，这种现象尚未在小鼠中进行系统分析。在这篇综述中，我们提出了小鼠基因敲除的例子，支持鲁棒性的概念，讨论了它可能已经演变的机制，以及推测其演变的原因。
In the field of mammalian functional genomics, one of the main aims in the post-genomic era is to elucidate the function of all genes in the genome. The powerful technology of gene targeting in embryonic stem cells has enabled the simple generation of mice lacking a specific gene. However, it is evident that in a proportion of such knockout mice no deviation in phenotype could be detected. Advancements in the field of mouse phenotyping and use of extensive phenotyping tests on each knockout showed that abnormal phenotypes were sometimes detected in physiological areas where they were not initially anticipated, or only manifested under certain conditions, emphasizing the need for careful phenotypic investigation. Nevertheless, the effect of some genes became evident only upon inactivation of another gene, pointing to the phenomenon of biological robustness. Unlike in yeast, this phenomenon has not yet been analysed systematically in the mouse. In this review, we present examples of mouse knockouts that lend support to the concept of robustness, discuss the mechanisms by which it may have evolved, as well as speculate on the reasons for its evolution.