Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

Abstract	Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function.
Authors	Y Okamoto, A Chaves, J Chen, R Kelley, K Jones, H G Weed, K L Gardner, L Gangi, M Yamaguchi, W Klomkleaw, T Nakayama, R L Hamlin, C Carnes, R Altschuld, J Bauer, T Hai
Journal	The American journal of pathology (Am J Pathol) Vol. 159 Issue 2 Pg. 639-50 (Aug 2001) ISSN: 0002-9440 [Print] United States
PMID	11485922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Activating Transcription Factor 3 Atf3 protein, rat Calcium-Binding Proteins Phosphoproteins SRI protein, human Sri protein, mouse Transcription Factors Myosin Heavy Chains
Topics	Activating Transcription Factor 3 Animals Calcium-Binding Proteins (genetics) Cardiomegaly (genetics, pathology, physiopathology) Cells, Cultured Disease Models, Animal Gene Expression Regulation Heart Conduction System (physiology) Humans Male Mice Mice, Transgenic Myocardial Contraction (genetics, physiology) Myocardial Ischemia (genetics, pathology, physiopathology) Myocardial Reperfusion Myocardium (pathology) Myosin Heavy Chains (genetics) Phosphoproteins (genetics) Promoter Regions, Genetic Rats Rats, Sprague-Dawley Transcription Factors (genetics, physiology)

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