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Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice
The site-specific recombinases Cre and Flp can mutate genes in a spatially and temporally restricted manner in mice. Conditional recombination of the tumor suppressor gene p53 using the Cre-loxP system has led to the development of multiple genetically engineered mouse models of human cancer. Howeve...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339833/ https://www.ncbi.nlm.nih.gov/pubmed/22228755 http://dx.doi.org/10.1242/dmm.009084 |
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author | Lee, Chang-Lung Moding, Everett J. Huang, Xiaofang Li, Yifan Woodlief, Loretta Z. Rodrigues, Rafaela C. Ma, Yan Kirsch, David G. |
author_facet | Lee, Chang-Lung Moding, Everett J. Huang, Xiaofang Li, Yifan Woodlief, Loretta Z. Rodrigues, Rafaela C. Ma, Yan Kirsch, David G. |
author_sort | Lee, Chang-Lung |
collection | PubMed |
description | The site-specific recombinases Cre and Flp can mutate genes in a spatially and temporally restricted manner in mice. Conditional recombination of the tumor suppressor gene p53 using the Cre-loxP system has led to the development of multiple genetically engineered mouse models of human cancer. However, the use of Cre recombinase to initiate tumors in mouse models limits the utilization of Cre to genetically modify other genes in tumor stromal cells in these models. To overcome this limitation, we inserted FRT (flippase recognition target) sites flanking exons 2–6 of the endogenous p53 gene in mice to generate a p53(FRT) allele that can be deleted by Flp recombinase. We show that FlpO-mediated deletion of p53 in mouse embryonic fibroblasts impairs the p53-dependent response to genotoxic stress in vitro. In addition, using FSF-Kras(G12D/+); p53(FRT/FRT) mice, we demonstrate that an adenovirus expressing FlpO recombinase can initiate primary lung cancers and sarcomas in mice. p53(FRT) mice will enable dual recombinase technology to study cancer biology because Cre is available to modify genes specifically in stromal cells to investigate their role in tumor development, progression and response to therapy. |
format | Online Article Text |
id | pubmed-3339833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-33398332012-05-02 Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice Lee, Chang-Lung Moding, Everett J. Huang, Xiaofang Li, Yifan Woodlief, Loretta Z. Rodrigues, Rafaela C. Ma, Yan Kirsch, David G. Dis Model Mech Resource Article The site-specific recombinases Cre and Flp can mutate genes in a spatially and temporally restricted manner in mice. Conditional recombination of the tumor suppressor gene p53 using the Cre-loxP system has led to the development of multiple genetically engineered mouse models of human cancer. However, the use of Cre recombinase to initiate tumors in mouse models limits the utilization of Cre to genetically modify other genes in tumor stromal cells in these models. To overcome this limitation, we inserted FRT (flippase recognition target) sites flanking exons 2–6 of the endogenous p53 gene in mice to generate a p53(FRT) allele that can be deleted by Flp recombinase. We show that FlpO-mediated deletion of p53 in mouse embryonic fibroblasts impairs the p53-dependent response to genotoxic stress in vitro. In addition, using FSF-Kras(G12D/+); p53(FRT/FRT) mice, we demonstrate that an adenovirus expressing FlpO recombinase can initiate primary lung cancers and sarcomas in mice. p53(FRT) mice will enable dual recombinase technology to study cancer biology because Cre is available to modify genes specifically in stromal cells to investigate their role in tumor development, progression and response to therapy. The Company of Biologists Limited 2012-05 2011-12-22 /pmc/articles/PMC3339833/ /pubmed/22228755 http://dx.doi.org/10.1242/dmm.009084 Text en © 2012. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms |
spellingShingle | Resource Article Lee, Chang-Lung Moding, Everett J. Huang, Xiaofang Li, Yifan Woodlief, Loretta Z. Rodrigues, Rafaela C. Ma, Yan Kirsch, David G. Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice |
title | Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice |
title_full | Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice |
title_fullStr | Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice |
title_full_unstemmed | Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice |
title_short | Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice |
title_sort | generation of primary tumors with flp recombinase in frt-flanked p53 mice |
topic | Resource Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339833/ https://www.ncbi.nlm.nih.gov/pubmed/22228755 http://dx.doi.org/10.1242/dmm.009084 |
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