Over the past two decades the techniques associated with the manipulation o
f the mouse genome have provided a powerful approach toward the better unde
rstanding of gene function. Conventional transgenic and gene targeting appr
oaches have been used extensively, and these techniques have been particula
rly rewarding for neuroscientists. Nevertheless, the traditional approaches
toward genome manipulation have certain limitations that diminish their us
efulness for studying more sophisticated biological processes. Therefore, V
ariations to these techniques have recently been developed. The improvement
s are focused on two areas: one provides regulated control of transgene exp
ression using an inducible expression system; and the other provides the op
portunity to inactivate genes in specific cells and at predetermined develo
pmental stages with a conditional gene targeting system. This review summar
izes the advantages as well as some of the technical difficulties of these
new approaches. The application of these advanced approaches in biomedical
research, particularly neuroscience, are also discussed.