Saveliev Alexander, Tybulewicz Victor L J
Medical Research Council National Institute for Medical Research, London, UK.
Nat Immunol. 2009 Apr;10(4):361-4. doi: 10.1038/ni.1709. Epub 2009 Mar 19.
The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Although this gene 'knockout' approach is often informative, in many cases, the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data.
基因靶向技术的出现极大地促进了淋巴细胞信号传导的分析，该技术可实现单个基因的选择性失活。尽管这种基因“敲除”方法常常能提供有用信息，但在许多情况下，基因敲除所导致的表型可能无法完整呈现相应蛋白质的功能。如果一种蛋白质在单个或多个信号通路中具有多种功能，或者在复合物中稳定其他蛋白质，那么基因敲除的表型后果可能表现为几种不同扰动的组合。在这些情况下，通过基因靶向“敲入”细微的点突变可能会更准确地洞察蛋白质功能。然而，为了获得有用信息，此类突变必须仔细地基于结构和生物物理数据。
