Cardiac fibrosis in mice expressing an inducible myocardial-specific Cre driver
Open Access
- 1 January 2013
- journal article
- Published by The Company of Biologists in Disease Models & Mechanisms
- Vol. 6 (6), 1470-6
- https://doi.org/10.1242/dmm.010470
Abstract
Summary Tamoxifen-inducible Cre-mediated manipulation of animal genomes has achieved wide acceptance over the last decade, with numerous important studies heavily relying on this technique. Recently, a number of groups have reported transient complications of using this protocol in the heart. In the present study we observed a previously unreported focal fibrosis and depressed left-ventricular function in tamoxifen treated αMHC-MerCreMer-positive animals in a Tβ4shRNAflox x αMHC-MerCreMer cross at 6-7 weeks following standard tamoxifen treatment, regardless of the presence of the floxed transgene. The phenotype was reproduced by treating mice from the original αMHC-MerCreMer strain with tamoxifen. In the acute phase after tamoxifen treatment, cell infiltration into the myocardium was accompanied by increased expression of pro-inflammatory cytokines (IL-1β, IL-6, TNFα, IFNγ, Ccl2) and markers of hypertrophy (ANF, BNP, Col3a1). These observations highlight the requirement for including tamoxifen-treated MerCreMer littermate controls to avert misinterpretation of conditional mutant phenotypes. A survey of the field as well as the protocols presented here suggests that controlling the parameters of tamoxifen delivery is important in avoiding the chronic MerCreMer-mediated cardiac phenotype reported here.Keywords
This publication has 22 references indexed in Scilit:
- A robust and high-throughput Cre reporting and characterization system for the whole mouse brainNature Neuroscience, 2009
- Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 geneJournal of Molecular and Cellular Cardiology, 2009
- Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and functionProceedings of the National Academy of Sciences of the United States of America, 2009
- Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injuryNature Medicine, 2007
- The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stressNature Medicine, 2007
- Cryptic loxP sites in mammalian genomes: genome-wide distribution and relevance for the efficiency of BAC/PAC recombineering techniquesNucleic Acids Research, 2007
- Optimization of spatiotemporal gene inactivation in mouse heart by oral application of tamoxifen citrategenesis, 2007
- Kinetics of tamoxifen‐regulated Cre activity in mice using a cartilage‐specific CreERT to assay temporal activity windows along the proximodistal limb skeletonDevelopmental Dynamics, 2006
- Growth inhibition and DNA damage induced by Cre recombinase in mammalian cellsProceedings of the National Academy of Sciences of the United States of America, 2001
- Inducible Site-Directed Recombination in Mouse Embryonic Stem CellsNucleic Acids Research, 1996