Wilder P J, Rizzino A
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Cytotechnology. 1993;11(2):79-99. doi: 10.1007/BF00748997.
Over 1500 mouse mutants have been identified, but few of the genes responsible for the defects have been identified. Recent developments in the area of gene targeting are revolutionizing the field of mouse genetics and our understanding of numerous genes, including those thought to be involved in cell proliferation and differentiation. Gene targeting was developed as a method for producing a predetermined mutation in a specific endogenous gene. Advances in the design of targeting vectors and in the use of embryonic stem cells have permitted the production of numerous mutant mice with null mutations in specific genes. These mutant mice will be critical for investigating the in vivo functions of many genes that have been cloned in recent years. This review discusses a wide range of new developments in the field of gene targeting with a focus on issues to be considered by those planning to use this new technology. It also examines some of the lessons learned from recent gene targeting studies and discusses different applications of the technology that are likely to generate scores of new animal models for a wide range of human diseases.
已鉴定出1500多种小鼠突变体，但导致这些缺陷的基因却鲜有被鉴定出来的。基因靶向领域的最新进展正在彻底改变小鼠遗传学领域以及我们对众多基因的理解，包括那些被认为参与细胞增殖和分化的基因。基因靶向技术是作为一种在特定内源基因中产生预定突变的方法而开发的。靶向载体设计和胚胎干细胞使用方面的进展使得能够产生许多在特定基因中具有无效突变的突变小鼠。这些突变小鼠对于研究近年来克隆的许多基因的体内功能至关重要。本综述讨论了基因靶向领域的一系列新进展，重点关注计划使用这项新技术的人员需要考虑的问题。它还审视了从最近的基因靶向研究中吸取的一些经验教训，并讨论了该技术的不同应用，这些应用可能会为广泛的人类疾病生成大量新的动物模型。
