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Vol. 54, Issue 3, 495-503, September 1998
Laboratory of Molecular Psychiatry and Center for Genes and
Behavior, Departments of Psychiatry and Neurobiology, Yale University
School of Medicine, New Haven, Connecticut 06508 (J.C., M.B.K, G.Z.,
N.S., C.S., M.R.P., R.S.D., E.J.N.) and
Section of Immunobiology, Yale
University School of Medicine, New Haven, Connecticut 06520 (P.E.S.)
Several inducible gene expression systems have been developed in
vitro in recent years to overcome limitations with traditional transgenic mice. One of these, the tetracycline-regulated system, has
been used successfully in vivo. Nevertheless, concerns
remain about the ability of this system to direct high levels of
transgene expression in vivo and to
enable such expression to be turned on and off effectively. We report
here the generation, using a modified tetracycline-regulated system
under the control of the neuron-specific enolase promoter, of several
lines of mice that direct transgene expression to specific brain
regions, including the striatum, cerebellum, CA1 region of the
hippocampus, or deep layers of cerebral neocortex. Transgene expression
in these mice can be turned off completely with low doses of
doxycycline (a tetracycline derivative) and driven to very high levels
in the absence of doxycycline. We demonstrate this tissue-specific,
inducible expression for three transgenes: those that encode luciferase (a reporter protein) or 
FosB or the cAMP-response element binding protein (CREB) (two transcription factors). The various lines of
transgenic mice demonstrate an inducible system that generates high
levels of transgene expression in specific brain regions and represent
novel and powerful tools with which to study the functioning of these
(or potentially any other) genes in the brain.
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