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

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Title: Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen
Author(s): Benedykcinska, A
Ferreira, A
Lau, J
Broni, J
Richard-Loendt, A
Henriquez, NV
Brandner, S
Item Type: Journal Article
Abstract: © 2016 Published by The Company of Biologists Ltd.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.
Publication Date: 2-Feb-2016
Date of Acceptance: 21-Dec-2015
URI: http://hdl.handle.net/10044/1/36636
DOI: https://dx.doi.org/10.1242/dmm.022715
ISSN: 1754-8403
Publisher: The Company of Biologists Ltd
Start Page: 211
End Page: 220
Journal / Book Title: Disease Models and Mechanisms
Volume: 9
Issue: 2
Copyright Statement: © 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://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Brain tumour
Cre recombination
Endoxifen
Tamoxifen
loxP system
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Conference Place: England
Appears in Collections:Genomics of Common Disease



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