Inducible cardiomyocyte-specific gene disruption directed by the rat Tnnt2 promoter in the mouse.
Inducible cardiomyocyte-specific gene disruption directed by the rat Tnnt2 promoter in the mouse.
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作者：
Wu, Bingruo;Zhou, Bin;Wang, Yidong;Cheng, Hsiu-Ling;Hang, Calvin T.;Pu, William T.;Chang, Ching-Pin;Zhou, Bin
我们开发了一种有条件的、可诱导的基因敲除方法，允许在小鼠心肌细胞中进行有效的基因缺失。该转基因小鼠系通过共注射两种转基因产生，一个是由大鼠心肌肌钙蛋白T(TnNT2)启动子控制的四环素控制反式激活子(RTTA)，另一个是由四环素反应启动子(Teto)驱动的Cre重组酶。在这里，Tnnt2-RTTA激活的Teto-Cre表达发生在多西环素治疗后的心肌细胞中。使用两个不同的小鼠Cre报告基因系，我们证明了在多西环素诱导下，Cre重组酶在胚胎或成年心脏的心肌细胞中被特异性地和强有力地诱导表达，从而允许心肌细胞特异性的基因中断和谱系追踪。我们还表明，RTTA的表达和多西环素治疗不会损害心功能。这些特点使得Tnnt2-RTTA；Teto-Cre转基因系成为分析发育和出生后心肌细胞的时空基因功能和谱系的有价值的遗传工具。
We developed a conditional and inducible gene knockout methodology that allows effective gene deletion in mouse cardiomyocytes. This transgenic mouse line was generated by co-injection 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.
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影响因子：
10.4
作者：
Zhou, B;Bi, YY;Han, ZC
通讯作者：
Han, ZC
影响因子：
20.1
作者：
Yu, ZH;Redfern, CS;Fishman, GI
通讯作者：
Fishman, GI
影响因子：
20.1
作者：
Wang, Q;Sigmund, CD;Lin, JJC
通讯作者：
Lin, JJC
影响因子：
10.5
作者：
Jiao, K;Kulessa, H;Hogan, BLM
通讯作者：
Hogan, BLM
DOI：
10.1002/gene.10022
发表时间：
2001-12-01
期刊：
Genesis The Journal of Genetics and Development
影响因子：
--
作者：
Moses, Kelvin A.;DeMayo, Franco;Schwartz, Robert J.
通讯作者：
Schwartz, Robert J.