Genetically modified mice-successes and failures of a widely used technology

Genetically modified mice, created by random integration of a transgene into the genome or by targeted mutation of a specific gene, have proven to be extremely powerful tools for studying gene function in vivo. In this article, we give (1) a short overview of the traditional methods in mouse transgenesis and (2) a discussion of the problems with these methods, (3) more recent methods that were developed to overcome these problems, and (4) an outlook on future directions in gene targeting.