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Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen

Benedykcinska, A; Ferreira, A; Lau, J; Broni, J; Richard-Loendt, A; Henriquez, NV; Brandner, S; (2016) Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen. Disease, Models & Mechanisms , 9 (2) pp. 211-220. 10.1242/dmm.022715. Green open access

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Abstract

Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS) can be limited, when the promoter (such as GFAP) is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER) allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours.

Type: Article
Title: Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dmm.022715
Publisher version: http://dx.doi.org/10.1242/dmm.022715
Language: English
Additional information: © 2016. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, http://www.creativecommons.org/licenses/by/3.0
Keywords: Brain tumour, Cre recombination, Endoxifen, Tamoxifen, loxP system
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre
URI: http://discovery.ucl.ac.uk/id/eprint/1477177
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