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Status: Bibliographieeintrag

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Verfasst von:Weber, Tillmann [VerfasserIn]   i
 Bartsch, Dusan [VerfasserIn]   i
Titel:Tetracycline inducible gene manipulation in serotonergic neurons
Verf.angabe:Tillmann Weber, Insa Renzland, Max Baur, Simon Mönks, Elke Herrmann, Verena Huppert, Frank Nürnberg, Kai Schönig, Dusan Bartsch
E-Jahr:2012
Jahr:May 31, 2012
Umfang:14 S.
Fussnoten:Gesehen am 30.04.2018
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2012
Band/Heft Quelle:7(2012,5) Artikel-Nummer e38193, 14 Seiten
ISSN Quelle:1932-6203
Abstract:The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a transgenic mouse tTA line (TPH2-tTA) which allows both inducible and reversible transgene expression and inducible Cre-mediated gene deletion selectively in 5-HT neurons throughout life. This will allow precise delineation of serotonergic gene functions during development and adulthood.
DOI:doi:10.1371/journal.pone.0038193
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kostenfrei: Volltext: http://dx.doi.org/10.1371/journal.pone.0038193
 kostenfrei: Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038193
 DOI: https://doi.org/10.1371/journal.pone.0038193
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Brainstem
 Deletion mutation
 Gene expression
 Genetically modified animals
 Immunohistochemistry techniques
 Mouse models
 Neurons
 Red nucleus
K10plus-PPN:1572492104
Verknüpfungen:→ Zeitschrift

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