Elimination of background recombination: somatic induction of Cre by combined transcriptional regulation and hormone binding affinity

Nucleic Acids Research
Richard KempDouglas J Winton

Abstract

Somatically inducible Cre lines are used extensively to study gene function. However, a background level of spontaneous recombination due to unregulated expression of Cre is particularly confounding for cancer models in which following the pathogenesis of the disease requires the introduction of sporadic mutations that are monitored over time. In three transgenic mouse lines, two with Cre activity controlled at the transcriptional level (Ahcre, Mx1cre), and one controlled at the protein level (R26creER(T)), we have identified sporadic recombination at the R26R reporter locus in multiple tissues. Detailed analysis of the intestinal epithelium suggests that recombination can occur both during development and as an ongoing process in adult life. Here we present a new inducible Cre transgenic line, AhcreER(T), in which control of Cre activity is regulated at two levels: by transcriptional control of the Ah promoter and by a requirement for Tamoxifen binding. There is no detectable background intestinal recombination in adult AhcreER(T) mice on the R26R background. Inducible and dose-dependent recombination can be achieved by a single combined treatment with beta-napthoflavone and Tamoxifen.

References

Sep 8, 1995·Science·R KühnK Rajewsky
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·R FeilP Chambon
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·A KistnerH Bujard
Dec 23, 1999·The Journal of Biological Chemistry·J R Saam, J I Gordon
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·M H WongJ I Gordon
Oct 5, 2001·Nature Reviews. Genetics·M Lewandoski
Feb 9, 2002·Genesis : the Journal of Genetics and Development·Caiying GuoCorrinne G Lobe
Feb 22, 2002·Genesis : the Journal of Genetics and Development·Kin-Ming Kwan
May 11, 2002·Nature Reviews. Cancer·Jos Jonkers, Anton Berns
Dec 6, 2002·Nucleic Acids Research·Kai SchönigHermann Bujard
Jan 17, 2003·American Journal of Physiology. Renal Physiology·André SchneiderMatthew D Breyer
Nov 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Stephanos KyrkanidesHoward J Federoff
Jan 16, 2004·Developmental Cell·Catherine S Branda, Susan M Dymecki

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Citations

Aug 29, 2012·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Stephen A MurrayNadia Rosenthal
Aug 6, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ramasamy PaulmuruganSanjiv S Gambhir
Nov 23, 2013·Science·Louis VermeulenDouglas J Winton
Sep 5, 2012·BMC Biology·Kai SchönigDusan Bartsch
Nov 28, 2013·Cancer & Metabolism·Liang ZhengEyal Gottlieb
Dec 23, 2011·Development·Emma J StringerFelix Beck
Aug 10, 2013·Disease Models & Mechanisms·Jonas LexowNadia Rosenthal
Mar 20, 2009·PLoS Biology·Amit J SabnisBenjamin S Braun
Feb 7, 2009·PloS One·Anne-Cécile Petit, Jean-François Nicolas
Oct 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ramasamy Paulmurugan, Sanjiv S Gambhir
Aug 10, 2007·Nature Reviews. Cancer·Kristopher K Frese, David A Tuveson
Apr 13, 2007·Expert Review of Anticancer Therapy·Victoria Marsh, Alan Clarke
Mar 10, 2016·Nature Communications·Maartje van der HeijdenLouis Vermeulen
Apr 9, 2008·Genesis : the Journal of Genetics and Development·Nicolas JullienJean-Paul Herman
Mar 3, 2007·Genesis : the Journal of Genetics and Development·Cara K BradleyJ Anke M van Eekelen
Mar 14, 2013·The Journal of Pathology·Victoria MarshAlan R Clarke
Jun 2, 2012·The Journal of Pathology·Lisa H MoyesPeter D Adams
Dec 17, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Frédéric P Lemaigre
Jan 24, 2012·Cell·Kai Kretzschmar, Fiona M Watt
Apr 2, 2014·Cell Reports·Je-Hoon SongKwang-Hyun Cho
Mar 29, 2008·Cell Stem Cell·Philip H JonesFiona M Watt
Nov 10, 2013·The American Journal of Pathology·Victoria Marsh DurbanAlan R Clarke
Oct 1, 2014·Blood·Talia Velasco-HernandezJörg Cammenga
Aug 23, 2016·Nature Cell Biology·Julia FredePhilip H Jones
Apr 9, 2017·Acta histochemica·Hongjie JiYujun Shi
Feb 8, 2013·Nature Reviews. Cancer·Maria P Alcolea, Philip H Jones
Aug 5, 2015·The EMBO Journal·David J HuelsOwen J Sansom
Feb 5, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cheryl D ZimberlinJan-Hermen Dannenberg
Jul 27, 2005·Biochemical Society Transactions·A R Clarke

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