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Titolo:
Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene expression
Autore:
Bruneau, BG; Bao, ZZ; Fatkin, D; Xavier-Neto, J; Georgakopoulos, D; Maguire, CT; Berul, CI; Kass, DA; Kuroski-de Bold, ML; de Bold, AJ; Conner, DA; Rosenthal, N; Cepko, CL; Seidman, CE; Seidman, JG;
Indirizzi:
Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ch Med, Dept Genet, Boston, MA 02115 USA Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 rd Hughes Med Inst, Boston, MA 02115 USA Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 ardiovasc, Boston, MA 02115 USA Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 Med Inst, Boston, MA 02115 USA Childrens Hosp, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115Childrens Hosp, Boston, MA 02115 USA Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA Massachusetts Gen Hosp Charlestown MA USA c Res Ctr, Charlestown, MA USA FMUSP, HC, Inst Coracao, InCor,Lab Genet & Cardiol Mol, BR-05403000 Sao Paulo, Brazil FMUSP Sao Paulo Brazil BR-05403000 BC Mol, BR-05403000 Sao Paulo, Brazil Johns Hopkins Univ, Baltimore, MD USA Johns Hopkins Univ Baltimore MD USA ohns Hopkins Univ, Baltimore, MD USA Univ Ottawa, Ottawa Hosp, Inst Heart, Ottawa, ON K1Y 4H9, Canada Univ Ottawa Ottawa ON Canada K1Y 4H9 st Heart, Ottawa, ON K1Y 4H9, Canada
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 5, volume: 21, anno: 2001,
pagine: 1730 - 1736
SICI:
0270-7306(200103)21:5<1730:CIIMIP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
BHLH TRANSCRIPTION FACTOR; MYOSIN LIGHT CHAIN-2; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; NATRIURETIC FACTOR GENE; HEART DEVELOPMENT; CARDIAC MORPHOGENESIS; IROQUOIS COMPLEX; XENOPUS HOMOLOG; TRANSGENIC MICE; MOUSE HEART;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Seidman, JG Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA Harvard Univ 200 Longwood Ave Boston MA USA 02115 MA 02115 USA
Citazione:
B.G. Bruneau et al., "Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene expression", MOL CELL B, 21(5), 2001, pp. 1730-1736

Abstract

To define the role of Irx4, a member of the Iroquois family of homeobox transcription factors in mammalian heart development and function, we disrupted the murine Irx4 gene. Cardiac morphology in Irx4-deficient mice (designated Irx4(Delta ex2/Delta ex2)) was normal during embryogenesis and in earlypostnatal life. Adult Irx4(Delta ex2/Delta ex2) mice developed a cardiomyopathy characterized by cardiac hypertrophy and impaired contractile function. Prior to the development of cardiomyopathy, Irx4(Delta ex2/Delta ex2) hearts had abnormal ventricular gene expression: Irx4-deficient embryos exhibited reduced ventricular expression of the basic helix-loop-helix transcription factor eHand (Hand1), increased Irx2 expression, and ventricular induction of an atrial chamber-specific transgene. In neonatal hearts, ventricular expression of atrial natriuretic factor and alpha -skeletal actin was markedly increased. Several weeks subsequent to these changes in embryonic and neonatal gene expression, increased expression of hypertrophic markers BNP and beta -myosin heavy chain accompanied adult-onset cardiac hypertrophy. Cardiac expression of Irx1, Irx2, and Irx5 may partially compensate for loss of Irx4 function. We conclude that Irx4 is not sufficient for ventricular chamber formation but is required far the establishment of some components of a ventricle-specific gene expression program. In the absence of genes under the control of Irx4, ventricular function deteriorates and cardiomyopathy ensues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 01:26:15