“Cre”-ating mouse mutants—a meeting review on conditional mouse genetics

So you want to make a mouse mutation to study the function of your favorite gene? Making a simple knockout is just the first step. The future is in complex genome engineering strategies that will allow you to knockout or misexpress your gene when and where you want, make a series of allelic alterations, and rearrange the chromosomal context in which the gene resides. However, undertaking this kind of analysis in mice is time-consuming and expensive. Many such strategies involve multiple components, each of which has to be tried and tested in a living animal. Everyone wants to know which systems work, but everyone hopes someone else will do the necessary groundwork to test them out. No wonder, then, that there was a large and attentive audience at a recent National Cancer Institute-sponsored workshop at Cold Spring Harbor Laboratory on Conditional Genetic Technologies in the Mouse, (August 31–September 2, 1998), all hoping to learn the latest successes in this area. They were treated to a series of talks by expert practioners in the field, who not only presented their success stories but also some of the problems and failures that do not make it into the published literature. Most of the talks and their accompanying slides can be accessed online athttp://www.leadingstrand.org/.

Although there is enormous potential in this area, the workshop clearly revealed that there is no fully developed, guaranteed successful kit of genetic reagents for creating conditional alterations. One reagent, however, can be considered out of the development phase and into the catalog of standard genetic tools. That reagent is, of course, the site-specific recombinase Cre. The Cre recombinase can excise DNA sequences between two loxP recognition sequences at a very high efficiency either in mammalian cells in culture or in mice. Tissue-specific gene knockout can be …