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In this study, we describe a novel model of heart failure based on cardiac\u2010specific deletion of the prototypical mammalian BAR adapter\u2010encoding gene <jats:italic>Bin1<\/jats:italic>, a modifier of age\u2010associated disease. <jats:italic>Bin1<\/jats:italic> deletion during embryonic development causes hypertrophic cardiomyopathy and neonatal lethality, but there is little information on how <jats:italic>Bin1<\/jats:italic> affects cardiac function in adult animals. Here we report that cardiomyocyte\u2010specific loss of <jats:italic>Bin1<\/jats:italic> causes age\u2010associated dilated cardiomyopathy (DCM) beginning by 8\u201310 months of age. Echocardiographic analysis showed that <jats:italic>Bin1<\/jats:italic> loss caused a 45% reduction in ejection fraction during aging. Younger animals rapidly developed DCM if cardiac pressure overload was created by transverse aortic constriction. Heterozygotes exhibited an intermediate phenotype indicating <jats:italic>Bin1<\/jats:italic> is haplo\u2010insufficient to sustain normal heart function. <jats:italic>Bin1<\/jats:italic> loss increased left ventricle (LV) volume and diameter during aging, but it did not alter LV volume or diameter in hearts from heterozygous mice nor did it affect LV mass. <jats:italic>Bin1<\/jats:italic> loss increased interstitial fibrosis and mislocalization of the voltage\u2010dependent calcium channel Ca<jats:sub>v<\/jats:sub>1.2, and the lipid raft scaffold protein caveolin\u20103, which normally complexes with Bin1 and Ca<jats:sub>v<\/jats:sub>1.2 in cardiomyocyte membranes. Our findings show how cardiac deficiency in Bin1 function causes age\u2010 and stress\u2010associated heart failure, and they establish a new preclinical model of this terminal cardiac disease. J. Cell. Biochem. 116: 2541\u20132551, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25198","type":"journal-article","created":{"date-parts":[[2015,5,2]],"date-time":"2015-05-02T22:23:00Z","timestamp":1430605380000},"page":"2541-2551","source":"Crossref","is-referenced-by-count":33,"title":["Cardiac\u2010Specific Disruption of Bin1 in Mice Enables a Model of Stress\u2010 and Age\u2010Associated Dilated Cardiomyopathy"],"prefix":"10.1002","volume":"116","author":[{"given":"Lisa D.","family":"Laury\u2010Kleintop","sequence":"first","affiliation":[{"name":"Lankenau Institute for Medical Research Wynnewood Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Mulgrew","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research Wynnewood 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