Conditional gene expression systems in the transgenic rat brain
- Equal contributors
1 Department of Molecular Biology, Central Institute of Mental Health and Heidelberg University, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany
2 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Heidelberg University, J5, 68159 Mannheim, Germany
3 German Cancer Research Center (DKFZ), Molecular Immunology, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
4 Zentrum für Molekulare Biologie Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
BMC Biology 2012, 10:77 doi:10.1186/1741-7007-10-77Published: 3 September 2012
Turning gene expression on and off at will is one of the most powerful tools for the study of gene function in vivo. While several conditional systems were successful in invertebrates, in mice the Cre/loxP recombination system and the tet-controlled transcription activation system are predominant. Both expression systems allow for spatial and temporal control of gene activities, and, in the case of tet regulation, even for the reversible activation/inactivation of gene expression. Although the rat is the principal experimental model in biomedical research, in particular in studies of neuroscience, conditional rat transgenic systems are exceptionally rare in this species.
We addressed this lack of technology, and established and thoroughly characterized CreERT2 and tTA transgenic rats with forebrain-specific transgene expression, controlled by the CaMKII alpha promoter. In addition, we developed new universal rat reporter lines for both transcription control systems and established inducible and efficient reporter gene expression in forebrain neurons.
We demonstrate that conditional genetic manipulations in the rat brain are both feasible and practicable and outline advantages and limitations of the Tet and Cre/loxP system in the rat brain.