Cardiac fibrosis in mice expressing an inducible myocardial-specific Cre driver

Jonas Lexow, Tommaso Poggioli, Padmini Sarathchandra, Maria Paola Santini, Nadia Alicia Rosenthal

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

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 alphaMHC-MerCreMer-positive animals in a Tbeta4shRNAflox x alphaMHC-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 alphaMHC-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-1beta, IL-6, TNFalpha, IFNgamma, 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.
Original languageEnglish
Pages (from-to)1470 - 1476
Number of pages7
JournalDisease Models and Mechanisms
Volume6
Issue number6
DOIs
Publication statusPublished - 2013

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