Transgenic Animals with Inducible, Targeted Gene Expression in Brain (original) (raw)
Research ArticleArticle
, Max B. Kelz, Guoqi Zeng, Norio Sakai, Cathy Steffen, Penny E. Shockett, Marina R. Picciotto, Ronald S. Duman and Eric J. Nestler
Molecular Pharmacology September 1998, 54 (3) 495-503; DOI: https://doi.org/10.1124/mol.54.3.495
Abstract
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 ΔFosB 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.
Footnotes
Received March 2, 1998.
Accepted May 18, 1998.
Send reprint requests to: Dr. Eric J. Nestler, Dept. of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508. E-mail: eric.nestler{at}qm.yale.edu
This work was supported by grants from the National Institute on Drug Abuse, National Institute of Mental Health, National Alliance for Research in Schizophrenia and Depression, and the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center, State of Connecticut Department of Mental Health and Addiction Services.
J.C. and M.B.K contributed equally to this work.
The American Society for Pharmacology and Experimental Therapeutics
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