Inducible and neuron-specific gene expression in the adult mouse brain with the rtTA2S-M2 system.
To achieve inducible and reversible gene expression in the adult mouse brain, we exploited an improved version of the tetracycline-controlled transactivator-based system (rtTA2(S)-M2, rtTA2 hereafter) and combined it with the forebrain-specific CaMKIIalpha promoter. Several independent lines of transgenic mice carrying the CaMKIIalpha promoter-rtTA2 gene were generated and examined for anatomical profile, doxycycline (dox)-dependence, time course, and reversibility of gene expression using several lacZ reporter lines. In two independent rtTA2-expressing lines, dox-treatment in the diet induced lacZ reporter expression in neurons of several forebrain structures including cortex, striatum, hippocampus, amygdala, and olfactory bulb. Gene expression was dose-dependent and was fully reversible. Further, a similar pattern of expression was obtained in three independent reporter lines, indicating the consistency of gene expression. Transgene expression could also be activated in the developing brain (P0) by dox-treatment of gestating females. These new rtTA2-expressing mice allowing inducible and reversible gene expression in the adult or developing forebrain represent useful models for future genetic studies of brain functions.
Michalon
Aubin
A
Brain Research Institute, Medical Faculty of University of Zürich, and Department of Biology of the Swiss Federal Institute of Technology, Switzerland.
Koshibu
Kyoko
K
Baumgärtel
Karsten
K
Spirig
Dominique Haingotiana
DH
Mansuy
Isabelle M
IM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C034811:tetracycline resistance-encoding transposon repressor protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004318:Doxycycline