naa a22 4500 528786946 20180924065502.0 cr unu---uuuuu 180924e20111129xx s 000 0 eng 10.3929/ethz-b-000045282 doi 10.1371/journal.pone.0028283 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/45282 Inducible Gene Manipulations in Brain Serotonergic Neurons of Transgenic Rats [Elektronische Daten] [Tillmann Weber, Kai Schönig, Björn Tews, Dusan Bartsch] PLoS ONE Open access ethresearch The serotonergic (5-HT) system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP), in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Weber Tillmann joint author Schönig Kai joint author Tews Björn joint author Bartsch Dusan joint author PLoS ONE s.l. : Public Library of Science 6 (11), p. e28283 1932-6203 http://hdl.handle.net/20.500.11850/45282 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/45282 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Weber Tillmann joint author ETHRESEARCH 700 1- Schönig Kai joint author ETHRESEARCH 700 1- Tews Björn joint author ETHRESEARCH 700 1- Bartsch Dusan joint author ETHRESEARCH 773 0- PLoS ONE s.l. : Public Library of Science 6 (11), p. e28283 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access