Müller U
Max-Planck-Institute for Brain Research, Deutschordenstr. 46, D-60528, Frankfurt, Germany.
Mech Dev. 1999 Apr;82(1-2):3-21. doi: 10.1016/s0925-4773(99)00021-0.
Gene targeting, defined as the introduction of site-specific modifications into the genome by homologous recombination, has revolutionarized the field of mouse genetics and allowed the analysis of diverse aspects of gene function in vivo. It is now possible to engineer specific genetic alterations ranging from subtle mutations to chromosomal rearrangements and more recently, even tissue-specific inducible gene targeting with temporo-spatial control has become feasible. This review tries to recapitulate what we have learned in this extremely rapidly expanding field during the past decade. Diverse aspects of the technique will be discussed starting from basic construct design to the analysis of complex phenotypes, including recent advances on inducible expression system. Many examples from different areas of biomedical research are given to illustrate the purpose and limitations of the employed experimental approaches.
基因打靶，即通过同源重组将位点特异性修饰引入基因组，它彻底改变了小鼠遗传学领域，并使得在体内分析基因功能的各个方面成为可能。现在，设计特定的基因改变已成为可能，这些改变范围从微小突变到染色体重排，最近，甚至具有时空控制的组织特异性诱导基因打靶也变得可行。本综述试图概括我们在过去十年中在这个极其迅速发展的领域所学到的知识。将从基本构建体设计开始讨论该技术的各个方面，直至复杂表型的分析，包括诱导表达系统的最新进展。给出了生物医学研究不同领域的许多例子，以说明所采用实验方法的目的和局限性。
