ABSTRACT
The ability to introduce precise changes into the germ line of mice has revolutionized our approach to investigating gene function in vivo. Despite its wide-ranging use, the technology is still relatively young, with the first engineered mice only created in the late 1980s. Since that time the experimental approaches used have rapidly evolved, and this chapter addresses some of the more recent advances in this technology. The simplest use of gene targeting has been the inactivation of a given allele in order to allow loss of function studies, and much effort has been focused on enhancing the efficiency of this process and in generating high-throughput protocols for gene inactivation. A second area of activity has been in exploring the potential of gene targeting to investigate gain-of-function and conditional mutations, and to precisely engineer chromosomes. Taken together with the established protocols for manipulating the germ line of the mouse, these approaches have opened the way for virtually any form of genetic change to be modeled in the mouse.
