Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy.

Disease Models & Mechanisms
Ellen DeesDavid M Bader

Abstract

CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly...Continue Reading

References

Jul 1, 1990·Statistics in Medicine·Y Hochberg, Y Benjamini
Nov 1, 1987·Journal of Molecular and Cellular Cardiology·S W Rabkin, P Sunga
Dec 1, 1982·The Journal of Cell Biology·D BaderD A Fischman
Feb 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J V PardoS W Craig
Aug 1, 1995·The Journal of Clinical Investigation·F MuntoniC Sewry
Jan 1, 1993·Cell Motility and the Cytoskeleton·J B RattnerT J Yen
Jul 1, 1996·Journal of Molecular and Cellular Cardiology·J F CollinsR A Walsh
Feb 1, 1997·Circulation Research·H TagawaG Cooper
Jun 1, 1997·The Journal of Clinical Investigation·M H SoonpaaL J Field
Mar 27, 1999·Journal of Molecular and Cellular Cardiology·X WangA M Gerdes
Mar 23, 2000·Cardiovascular Research·S HeinJ Schaper
Sep 7, 2000·The Journal of Clinical Investigation·S TsubataJ A Towbin
Mar 29, 2001·Journal of Molecular and Cellular Cardiology·T M OlsonV V Michels
Apr 13, 2001·European Journal of Pharmacology·K K ParkerB Atkinson
Nov 22, 2001·Lancet·W M FranzH A Katus
Jan 30, 2002·Circulation·Timothy M OlsonBrigitte M Jockusch
Jan 30, 2003·Trends in Cardiovascular Medicine·Jean-Claude PerriardElisabeth Ehler
Jun 28, 2003·The Journal of Biological Chemistry·Riichi ShibataJames S Trimmer
Oct 14, 2003·The Journal of Biological Chemistry·Mabelle AsheDavid Bader
Oct 22, 2003·Molecular Genetics and Metabolism·Bhagyalaxmi MohapatraNeil E Bowles
Mar 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Akihiko KomuroVincent T Marchesi
Jan 29, 2005·The Journal of Biological Chemistry·Xubin ZhouXueliang Zhu
May 20, 2005·The Journal of Laboratory and Clinical Medicine·Nadia N HanselGregory B Diette
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Victor SoukoulisDavid M Bader
Jul 28, 2005·The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology·Ellen DeesRichard L Goodwin
Nov 15, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Allen M Samarel
Mar 16, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Travis K Smith, David M Bader
Apr 8, 2006·Current Opinion in Cardiology·Michael H Gollob
May 5, 2006·Molecular Biology of the Cell·Ryan D PooleyDavid M Bader

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Citations

Jan 29, 2016·Human Mutation·Isabel FilgesPetter Strømme
Jun 24, 2015·The Journal of Cell Biology·Vladimir A VolkovJ Richard McIntosh
May 6, 2016·Molecular Biology of the Cell·Elise R PfaltzgraffDavid M Bader
Nov 9, 2018·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Chanell O HaleyD M Bader
Sep 11, 2018·Cell Cycle·Alessandro Berto, Valérie Doye
Sep 29, 2020·Frontiers in Physiology·Lingfei LiJiongyu Hu
Aug 3, 2017·Redox Biology·Justin M QuilesNamakkal S Rajasekaran

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