Hypertrophic cardiomyopathy in cardiac myosin binding protein-C knockout mice

Circulation Research
Samantha P HarrisRichard L Moss

Abstract

Familial hypertrophic cardiomyopathy (FHC) is an inherited autosomal dominant disease caused by mutations in sarcomeric proteins. Among these, mutations that affect myosin binding protein-C (MyBP-C), an abundant component of the thick filaments, account for 20% to 30% of all mutations linked to FHC. However, the mechanisms by which MyBP-C mutations cause disease and the function of MyBP-C are not well understood. Therefore, to assess deficits due to elimination of MyBP-C, we used gene targeting to produce a knockout mouse that lacks MyBP-C in the heart. Knockout mice were produced by deletion of exons 3 to 10 from the endogenous cardiac (c) MyBP-C gene in murine embryonic stem (ES) cells and subsequent breeding of chimeric founder mice to obtain mice heterozygous (+/-) and homozygous (-/-) for the knockout allele. Wild-type (+/+), cMyBP-C(+/-), and cMyBP-C(-/-) mice were born in accordance with Mendelian inheritance ratios, survived into adulthood, and were fertile. Western blot analyses confirmed that cMyBP-C was absent in hearts of homozygous knockout mice. Whereas cMyBP-C(+/-) mice were indistinguishable from wild-type littermates, cMyBP-C(-/-) mice exhibited significant cardiac hypertrophy. Cardiac function, assessed using ...Continue Reading

References

Feb 1, 1988·The Biochemical Journal·J L GarveyR J Solaro
Apr 1, 1985·Journal of Muscle Research and Cell Motility·R StarrG Offer
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A NagyJ C Roder
Jan 1, 1996·Molecular Biology of the Cell·S H SeilerL A Leinwand
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·A Weisberg, S Winegrad
Oct 14, 1998·The Journal of Clinical Investigation·Q YangJ Robbins
Sep 8, 1999·Human Mutation·P BrossN Gregersen
Nov 5, 1999·The Journal of Clinical Investigation·B K McConnellD H Fischman
May 18, 2001·American Journal of Physiology. Heart and Circulatory Physiology·J R PatelR L Moss

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Citations

May 13, 2010·Annals of Biomedical Engineering·Teresa T WangRichard J Gilbert
Jan 18, 2006·Heart Failure Reviews·Bradley M Palmer
Jan 18, 2006·Heart Failure Reviews·Audrey N Chang, James D Potter
Jun 19, 2010·Journal of Cardiovascular Translational Research·Rhian Shephard, Christopher Semsarian
Mar 23, 2011·Journal of Cardiovascular Translational Research·Steven B Marston
May 12, 2004·Molecular and Cellular Endocrinology·Melyssa R BrattonJose S Subauste
Feb 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Maria E ZoghbiRoger Craig
Mar 10, 2009·The Journal of Biological Chemistry·Justin F ShafferSamantha P Harris
Jan 25, 2011·The Journal of Biological Chemistry·Jeanne James, Jeffrey Robbins
Nov 26, 2003·The Journal of General Physiology·Irina KulikovskayaSaul Winegrad
May 2, 2007·The Journal of General Physiology·Irina KulikovskayaSaul Winegrad
Oct 29, 2008·The Journal of General Physiology·Maria V RazumovaSamantha P Harris
Jan 2, 2013·The Journal of General Physiology·Willem J de LangeJ Carter Ralphe
Dec 7, 2007·Cardiovascular Research·Sachio Morimoto
Jan 8, 2008·Cardiovascular Research·Thomas BurgoynePradeep K Luther
Jul 23, 2013·Human Molecular Genetics·Kyungsoo HaChristina A Gurnett
Nov 17, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Echoleah S RuferSusan M Smith
Sep 3, 2008·Clinical and Experimental Pharmacology & Physiology·Tatiana TsoutsmanChristopher Semsarian
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Kathleen A ClarkCarol C Gregorio
May 20, 2008·American Journal of Physiology. Heart and Circulatory Physiology·M Faadiel EssopLutfi Abu-Elheiga
Dec 14, 2011·Circulation. Cardiovascular Imaging·Candida L DesjardinsJulian E Stelzer
Mar 19, 2011·Circulation Research·Samantha P HarrisKristina L Bezold
May 21, 2011·Circulation Research·Sakthivel SadayappanJeffrey Robbins
May 4, 2010·BMC Medical Genetics·María Isabel Rodríguez-GarcíaManuel Hermida-Prieto
Nov 22, 2011·Stem Cell Research & Therapy·Tung-Ying Lu, Lei Yang
Apr 7, 2010·Journal of Lipid Research·Pawel DobrzynJames M Ntambi
Dec 7, 2013·Pflügers Archiv : European journal of physiology·Ranganath MamidiJulian E Stelzer
Dec 12, 2013·Pflügers Archiv : European journal of physiology·Diederik W D Kuster, Sakthivel Sadayappan
Jan 21, 2014·Pflügers Archiv : European journal of physiology·Carl W TongPaola C Rosas
Jul 19, 2012·Zygote : the Biology of Gametes and Early Embryos·Yan ZhuMan-Xi Jiang
Jan 31, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ji Young MunRoger Craig

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