Regional and Temporal Control of Genetic Manipulation in the Mouse

Abstract

With the deciphering of the human genome, a major challenge is to determine the function for each of the estimated 30,000 genes in the physiology and patho-physiology of various organs. Using the mouse as a model system, this has been achieved by new genetic tools that restrict genemanipulation in a regionaland time-specific manner, thus bypassing the lethality caused by the traditional gene targeting approach, which inactivates gene function in the whole body and/or during embryogenesis. The major systems for regional and temporal gene manipulation include site-specific recombinase (SSR) systems and inducible transcription systems (Branda and Dymecki 2004). Among these, the Cre-loxP SSR system, the Flp recombinase target (FRT) SSR system and the tetracycline (tet) regulatory systems are the most extensively used. Since the Cre-loxP and Flp-FRT system are quite similar in principle and methodology, in this chapter we will focus on the Cre-loxP, as well as the tet regulatory, system and describe their principles, applications, methodology and troubleshooting.