Cardiomyocyte-specific inactivation of transcription factor CREB in mice Marek Matus * , Geertje Lewin * , Frank Stümpel * , Igor B. Buchwalow † , Michael D. Schneider ‡ , Günther Schütz § , Wilhelm Schmitz * and Frank U. Müller * ,1 * Institute of Pharmacology and Toxicology and † Institute of Pathology, University of Münster, Münster, Germany; ‡ Department of Medicine, Center for Cardiovascular Development, Baylor College of Medicine, Houston, Texas, USA; § Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany 1 Correspondence: Institute of Pharmacology and Toxicology, University of Münster, Domagkstrasse 12, 48129 Münster, Germany. E-mail: mullerf@uni-muenster.de The transcription factor cAMP response element (CRE)-binding protein (CREB, Creb1 ) plays a critical role in regulating gene expression in response to activation of the cAMP-dependent signaling pathway, which is implicated in the pathophysiology of heart failure. Using the Cre- loxP system, we generated mice with a cardiomyocyte-specific inactivation of CREB and studied in this model whether CREB is critical for cardiac function. CREB-deficient mice were viable and displayed neither changes in cardiac morphology nor alterations of basal or isoproterenol-stimulated left ventricular function in vivo or of important cardiac regulatory proteins. Since CREB was proposed as a negative regulator of cardiomyocyte apoptosis by enhancing the expression of the antiapoptotic protein Bcl-2, we analyzed the fragmentation of DNA, the activity of caspases 3/7 and the expression of Bcl-2 and did not observe any differences between CREB-deficient and CREB-normal hearts. Our results suggest that the presence of CREB is not critical for normal cardiac function in mice.—Matus M., Lewin G., Stümpel F., Buchwalow I. B., Schneider M. D., Schütz G., Schmitz W., and Müller F. U. Cardiomyocyte-specific inactivation of transcription factor CREB in mice. Key Words: Cre-lox P system • knockout mice • cAMP responsive element binding protein • heart
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Cardiomyocyte-specific inactivation of transcription factor CREB in mice
Matus, Marek; Lewin, Geertje; Stümpel, Frank; Buchwalow, Igor B.; Schneider, Michael D.; Schütz, Günther; Schmitz, Wilhelm; Müller, Frank U.
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, Volume 21 (8): 1884
Fed of American Socs for Experimental Biology – Jun 1, 2007
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