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

B Wu, B Zhou, Y Wang, HL Cheng, CT Hang, WT Pu… - genesis, 2010 - Wiley Online Library
B Wu, B Zhou, Y Wang, HL Cheng, CT Hang, WT Pu, CP Chang, B Zhou
genesis, 2010Wiley Online Library
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 …
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 spatiotemporal gene function and cardiomyocyte lineage tracing during developmental and postnatal periods. genesis 48:63–72, 2010. © 2009 Wiley‐Liss, Inc.
Wiley Online Library