Inducible cardiomyocyte-specific gene disruption directed by the rat Tnnt2 promoter in the mouse

Bingruo Wu, Bin Zhou, Yidong Wang, Hsiu Ling Cheng, Calvin T. Hang, William T. Pu, Ching Pin Chang, Bin Zhou

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

We developed a conditional and inducible gene knockout methodology that allows effective gene deletion in mouse cardiomyocytes. This transgenic mouse line was generated by coinjection of two transgenes, a ''reverse'' tetracycline-controlled transactivator (rtTA) directed by a rat cardiac troponin T (Tnnt2) promoter and a Cre recombinase driven by a tetracycline-responsive promoter (TetO). Here, Tnnt2-rtTA activated TetO-Cre expression takes place in cardiomyocytes following doxycycline treatment. Using two different mouse Cre reporter lines, we demonstrated that expression of Cre recombinase was specifically and robustly induced in the cardiomyocytes of embryonic or adult hearts following doxycycline induction, thus, allowing cardiomyocyte-specific gene disruption and lineage tracing. We also showed that rtTA expression and doxycycline treatment did not compromise cardiac function. These features make the Tnnt2-rtTA;TetO-Cre transgenic line a valuable genetic tool for analysis of spatio-temporal gene function and cardiomyocyte lineage tracing during developmental and postnatal periods.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalGenesis
Volume48
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Cardiomyocyte
  • Cre recombinase
  • Doxycycline
  • Tnnt2
  • rtTA

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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