title: Cardiomyocyte-specific inactivation of transcription factor CREB in mice.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Münster, Domagkstrasse 12, 48129 Münster, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Matus
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
authors.forename: Frank
authors.initials: F
authors.lastname: Stümpel
authors.forename: Igor B
authors.initials: IB
authors.lastname: Buchwalow
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schneider
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schmitz
authors.forename: Frank U
authors.initials: FU
authors.lastname: Müller
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency / Q000502:physiology*; D053938:DNA Fragmentation; D006321:Heart / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D015996:Survival Rate; D014157:Transcription Factors; D016277:Ventricular Function, Left
chemical_list: D051017:Apoptosis Regulatory Proteins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors