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Inducible cardiomyocyte‐specific gene disruption directed by the rat Tnnt2 promoter in the mouse
Author(s) -
Wu Bingruo,
Zhou Bin,
Wang Yidong,
Cheng HsiuLing,
Hang Calvin T.,
Pu William T.,
Chang ChingPin,
Zhou Bin
Publication year - 2010
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20573
Subject(s) - cre recombinase , doxycycline , transgene , biology , genetically modified mouse , gene , gene targeting , gene expression , conditional gene knockout , microbiology and biotechnology , transactivation , reporter gene , promoter , genetics , phenotype , antibiotics
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 spatiotemporal gene function and cardiomyocyte lineage tracing during developmental and postnatal periods. genesis 48:63–72, 2010. © 2009 Wiley‐Liss, Inc.