Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability

Circulation Research
Toru OkaJeffery D Molkentin

Abstract

The transcription factor GATA4 is a critical regulator of cardiac gene expression where it controls embryonic development, cardiomyocyte differentiation, and stress responsiveness of the adult heart. Traditional deletion of Gata4 caused embryonic lethality associated with endoderm defects and cardiac malformations, precluding an analysis of the role of GATA4 in the adult myocardium. To address the function of GATA4 in the adult heart, Gata4-loxP-targeted mice (Gata4fl/fl) were crossed with mice containing a beta-myosin heavy chain (beta-MHC) or alpha-MHC promoter-driven Cre transgene, which produced viable mice that survived into adulthood despite a 95% and 70% loss of GATA4 protein, respectively. However, cardiac-specific deletion of Gata4 resulted in a progressive and dosage-dependent deterioration in cardiac function and dilation in adulthood. Moreover, pressure overload stimulation induced rapid decompensation and heart failure in cardiac-specific Gata4-deleted mice. More provocatively, Gata4-deleted mice were compromised in their ability to hypertrophy following pressure overload or exercise stimulation. Mechanistically, cardiac-specific deletion of Gata4 increased cardiomyocyte TUNEL at baseline in embryos and adults as t...Continue Reading

References

Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·T C HerzigB E Markham
May 18, 1999·Molecular and Cellular Biology·F CharronM Nemer
May 18, 2001·The Journal of Biological Chemistry·Q LiangJ D Molkentin
May 31, 2001·The Journal of Biological Chemistry·C MoriscoJ Sadoshima
Jan 10, 2002·Genesis : the Journal of Genetics and Development·K A MosesR J Schwartz
Dec 6, 2003·Circulation Research·Benjamin J WilkinsJeffery D Molkentin
Apr 15, 2004·The Journal of Biological Chemistry·Stephanie A ParsonsJeffery D Molkentin
Apr 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anne AriesMona Nemer
Jul 14, 2004·Cardiovascular Research·Sampsa PikkarainenHeikki Ruskoaho
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alistair J WattStephen A Duncan
Oct 7, 2004·Developmental Biology·William T PuSeigo Izumo
Dec 30, 2004·Journal of Molecular and Cellular Cardiology·Christopher P Baines, Jeffery D Molkentin
May 20, 2005·The Journal of Clinical Investigation·Elisabeth M ZeisbergWilliam T Pu

❮ Previous
Next ❯

Citations

Aug 13, 2011·American Journal of Medical Genetics. Part a·Joshua J BlinderJohn L Jefferies
Oct 29, 2013·Nature Cell Biology·Ellen DirkxLeon J De Windt
Jul 20, 2010·Nature Medicine·Joerg HeinekeJeffery D Molkentin
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Joerg Heineke, Jeffery D Molkentin
Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Douglas P MillayJeffery D Molkentin
Jul 13, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jop H van BerloJeffery D Molkentin
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Russell S WhelanRichard N Kitsis
Dec 29, 2009·The Journal of Biological Chemistry·Marjorie MailletJeffery D Molkentin
Jun 23, 2010·The Journal of Biological Chemistry·Joost J LeendersEsther E Creemers
Nov 6, 2010·The Journal of Biological Chemistry·Hiba KomatiMona Nemer
Dec 17, 2010·The Journal of Biological Chemistry·Arunima SenguptaKatherine E Yutzey
Jul 8, 2009·Stem Cells and Development·Shinka MiyamotoHiromi Kurosawa
Mar 13, 2008·Tissue Engineering. Part a·Valerie F Shimko, William C Claycomb
Nov 19, 2010·Cardiovascular Research·Ah-Mee ParkYuichiro J Suzuki
Jun 6, 2009·Human Molecular Genetics·Li Qian, Rolf Bodmer
Jan 21, 2011·Biology of Reproduction·Antti KyrönlahtiDavid B Wilson
Jun 15, 2010·The Journal of Pharmacology and Experimental Therapeutics·Saisudha KokaRakesh C Kukreja
Apr 5, 2012·Molecular and Cellular Biology·Joseph M GallagherBranko V Latinkić
Feb 4, 2009·Molecular and Cellular Biology·Sadakatsu IkedaWilliam T Pu
Aug 28, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Abir YamakMona Nemer
Oct 10, 2009·Circulation Research·Qinghang LiuJeffery D Molkentin
Jul 10, 2010·Circulation Research·Hiroyuki NakayamaJeffery D Molkentin
Aug 14, 2010·Circulation Research·Jop H van BerloJeffery D Molkentin
Feb 22, 2012·Circulation Research·Maha Abdellatif
Mar 10, 2012·Circulation Research·Qinghang LiuJeffery D Molkentin
Sep 1, 2012·Circulation Research·Jennifer DavisJeffery D Molkentin
Aug 19, 2007·The Journal of Clinical Investigation·Hiroyuki NakayamaJeffery D Molkentin
Nov 3, 2007·The Journal of Clinical Investigation·Joerg HeinekeJeffery D Molkentin
Sep 11, 2009·The Journal of Clinical Investigation·Marjorie MailletJeffery D Molkentin
May 5, 2009·The Journal of Clinical Investigation·Bin ZhouWilliam T Pu
Nov 19, 2009·The Journal of Clinical Investigation·Hiroyuki NakayamaJeffery D Molkentin
Dec 30, 2009·The Journal of Clinical Investigation·Chien-hui LiaoIssei Komuro
Nov 15, 2011·The Journal of Clinical Investigation·Tao ShenSylvia M Evans
Sep 26, 2012·The Journal of Clinical Investigation·Manuel CarrascoAnabel Rojas
Mar 31, 2012·Endocrinology·Justyna KrachulecDavid B Wilson
Oct 11, 2012·Development·Timothy M Chlon, John D Crispino
Sep 6, 2008·Circulation Journal : Official Journal of the Japanese Circulation Society·Toru Oka, Issei Komuro

❮ Previous
Next ❯

Related Concepts