Genomes and Genes
Gene Symbol: Myh6
Description: myosin, heavy polypeptide 6, cardiac muscle, alpha
Alias: A830009F23Rik, AA517445, Myhc-a, Myhca, alpha-MHC, alphaMHC, myosin-6, Myosin heavy chain, cardiac muscle alpha isoform (MyHC-alpha), alpha cardiac MHC, alpha myosin, cardiac myosin heavy chain alpha isoform, cardiomyopathy, hypertrophic 1, myHC-alpha, myosin heavy chain 6, myosin heavy chain, cardiac muscle, adult
- Trivedi C, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, et al. Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med. 2007;13:324-31 pubmed
- Kuo C, Morrisey E, Anandappa R, Sigrist K, Lu M, Parmacek M, et al. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 1997;11:1048-60 pubmed..However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis. ..
- Yin Z, Jones G, Towns W, Zhang X, Abel E, Binkley P, et al. Heart-specific ablation of Prkar1a causes failure of heart development and myxomagenesis. Circulation. 2008;117:1414-22 pubmed publisher..These biochemical changes lead to myxoma-like changes, indicating that these mice may be a good model with which to study the formation of these tumors. ..
- Hardt S, Geng Y, Montagne O, Asai K, Hong C, Yang G, et al. Accelerated cardiomyopathy in mice with overexpression of cardiac G(s)alpha and a missense mutation in the alpha-myosin heavy chain. Circulation. 2002;105:614-20 pubmed..05). These results show that the cardiomyopathy developed by G(s)alpha x403 mice is synergistic rather than additive, most likely owing to the elevated baseline function combined with enhanced responsiveness to sympathetic stimulation. ..
- Mhatre A, Li J, Kim Y, Coling D, Lalwani A. Cloning and developmental expression of nonmuscle myosin IIA (Myh9) in the mammalian inner ear. J Neurosci Res. 2004;76:296-305 pubmed..Identification of Myh9 in the developing and mature inner ear suggests a role for this protein in the development and maintenance of auditory function. ..
- Liu Y, Li B, Sun X, Lin A, Wang D. Effect of selenium on the interaction between daunorubicin and cardiac myosin. Biol Trace Elem Res. 2012;147:240-5 pubmed publisher..The data indicate that selenium in the form of sodium selenite at appropriate dosage (<10.0 ?g Se/ml) diminish the cardiac toxicity of DNR, potentially allowing the use of DNR at higher dosages in clinical cancer chemotherapy. ..
- Robbins J, Gulick J, Sanchez A, Howles P, Doetschman T. Mouse embryonic stem cells express the cardiac myosin heavy chain genes during development in vitro. J Biol Chem. 1990;265:11905-9 pubmed..These data indicate that EB transcribe the appropriate tissue- and developmental stage-specific myosin heavy chain genes and therefore serve as a model system for studying early cardiogenic processes at the molecular level. ..
- Kamiya K, Yum S, Kurebayashi N, Muraki M, Ogawa K, Karasawa K, et al. Assembly of the cochlear gap junction macromolecular complex requires connexin 26. J Clin Invest. 2014;124:1598-607 pubmed publisher..Our results demonstrate that deafness-associated mutations in CX26 induce the macromolecular degradation of large gap junction complexes accompanied by an increase in caveolar structures. ..
- Adolph E, Subramaniam A, Cserjesi P, Olson E, Robbins J. Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the alpha-cardiac myosin heavy chain gene. J Biol Chem. 1993;268:5349-52 pubmed..In addition, cardiac-specific expression of the transgene was perturbed with significant levels of ectopic expression occurring in the aorta. ..
- Han P, Li W, Lin C, Yang J, Shang C, Nuernberg S, et al. A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 2014;514:102-106 pubmed publisher..Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA-chromatin interaction. ..
- Semsarian C, Healey M, Fatkin D, Giewat M, Duffy C, Seidman C, et al. A polymorphic modifier gene alters the hypertrophic response in a murine model of familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001;33:2055-60 pubmed..We conclude that genetic modifiers in mice, and presumably in man, can alter the hypertrophic response to sarcomere protein gene missense mutations. ..
- Kruithof B, van den Hoff M, Tesink Taekema S, Moorman A. Recruitment of intra- and extracardiac cells into the myocardial lineage during mouse development. Anat Rec A Discov Mol Cell Evol Biol. 2003;271:303-14 pubmed..We show that prior to the expression of myocardial markers, alpha-Sma is expressed in these regions, which suggests that these mesodermal cells become recruited into the cardiac lineage after formation of the linear heart tube. ..
- Tsoutsman T, Kelly M, Ng D, Tan J, Tu E, Lam L, et al. Severe heart failure and early mortality in a double-mutation mouse model of familial hypertrophic cardiomyopathy. Circulation. 2008;117:1820-31 pubmed publisher..The presence of 2 disease-causing mutations may predispose individuals to a greater risk of developing severe heart failure than human FHC caused by a single gene mutation. ..
- Argao E, Kern M, Branford W, Scott W, Potter S. Malformations of the heart, kidney, palate, and skeleton in alpha-MHC-Hoxb-7 transgenic mice. Mech Dev. 1995;52:291-303 pubmed..Misexpression of Hoxb-7 during heart development may be involved in the pathogenesis of VSD. ..
- Kaneko Oshikawa C, Nakagawa T, Yamada M, Yoshikawa H, Matsumoto M, Yada M, et al. Mammalian E4 is required for cardiac development and maintenance of the nervous system. Mol Cell Biol. 2005;25:10953-64 pubmed..UFD2a thus appears to be essential for the development of cardiac muscle, as well as for the protection of spinocerebellar neurons from degeneration induced by endoplasmic reticulum stress. ..
- Lv H, Havari E, Pinto S, Gottumukkala R, Cornivelli L, Raddassi K, et al. Impaired thymic tolerance to ?-myosin directs autoimmunity to the heart in mice and humans. J Clin Invest. 2011;121:1561-73 pubmed publisher..Here, we show that the ?-isoform of myosin heavy chain (?-MyHC, which is encoded by the gene Myh6) is the pathogenic autoantigen for CD4+ T cells in a spontaneous mouse model of myocarditis...
- Appler J, Lu C, Druckenbrod N, Yu W, Koundakjian E, Goodrich L. Gata3 is a critical regulator of cochlear wiring. J Neurosci. 2013;33:3679-91 pubmed publisher..As the first auditory-specific regulator of SGN development, Gata3 provides a useful molecular entry point for efforts to engineer SGNs for the restoration of hearing. ..
- Lyons G, Schiaffino S, Sassoon D, Barton P, Buckingham M. Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol. 1990;111:2427-36 pubmed..This dynamic pattern of changes in the myosin phenotype in the prenatal mouse heart suggests that there are different regulatory mechanisms for cell-specific expression of myosin isoforms during cardiac development. ..
- McConnell B, Fatkin D, Semsarian C, Jones K, Georgakopoulos D, Maguire C, et al. Comparison of two murine models of familial hypertrophic cardiomyopathy. Circ Res. 2001;88:383-9 pubmed..Heterozygous mice bearing a cardiac MHC missense mutation (alphaMHC(403/+) or a cardiac MyBP-C mutation (MyBP-C(t/+)) were constructed as murine FHC models using homologous ..
- Olsson M, Palmer B, Leinwand L, Moore R. Gender and aging in a transgenic mouse model of hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2001;280:H1136-44 pubmed..Collectively, these results further underscore the potential utility of this transgenic mouse model in elucidating pathogenesis of FHC...
- Sadayappan S, Osinska H, Klevitsky R, Lorenz J, Sargent M, Molkentin J, et al. Cardiac myosin binding protein C phosphorylation is cardioprotective. Proc Natl Acad Sci U S A. 2006;103:16918-23 pubmed..These data demonstrate that cMyBP-C phosphorylation functions in maintaining thick filament spacing and structure and can help protect the myocardium from ischemic injury. ..
- Arora H, Boulberdaa M, Qureshi R, Bitirim V, Gasser A, Messaddeq N, et al. Prokineticin receptor-1 signaling promotes Epicardial to Mesenchymal Transition during heart development. Sci Rep. 2016;6:25541 pubmed publisher..Our mice provide genetic models for congenital dysfunction of the heart and should facilitate studies of both pathogenesis and therapy of cardiac disorders in humans. ..
- Colbert M, Kirby M, Robbins J. Endogenous retinoic acid signaling colocalizes with advanced expression of the adult smooth muscle myosin heavy chain isoform during development of the ductus arteriosus. Circ Res. 1996;78:790-8 pubmed..These data suggest that RA may play a role in inducing and maintaining smooth muscle differentiation in the developing ductus arteriosus and may promote precocious expression of the adult vascular phenotype. ..
- Traystman M, Chow L, McManus B, Herskowitz A, Nesbitt M, Beisel K. Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14. Am J Pathol. 1991;138:721-6 pubmed..D2(57N) H-8b congenic mice supported this linkage relationship. Analysis of the AXB/BXA RI strain distribution patterns suggested that amd maps distal to the Np-2, Tcr alpha, and Myhc alpha loci.
- Banerjee I, Zhang J, Moore Morris T, Lange S, Shen T, Dalton N, et al. Thymosin beta 4 is dispensable for murine cardiac development and function. Circ Res. 2012;110:456-64 pubmed publisher..5-Cre and ?MHC-Cre, were also found to have no phenotype. We conclude that T?4 is dispensable for embryonic viability, heart development, coronary vessel development, and adult myocardial function. ..
- Huang Z, Young Seok H, Zhou B, Chen J, Chen J, Tao Y, et al. CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy. Circ Res. 2012;110:818-30 pubmed publisher..Most importantly, overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy. Our studies therefore identify CIP as a novel regulator of cardiac hypertrophy. ..
- Bevilacqua L, Maguire C, Seidman J, Seidman C, Berul C. QT dispersion in alpha-myosin heavy-chain familial hypertrophic cardiomyopathy mice. Pediatr Res. 1999;45:643-7 pubmed..It also suggests that although gender- and genotype-specific QTd values are increased, they do not predict arrhythmia risk in FHC mice. ..
- Wolf C, Moskowitz I, Arno S, Branco D, Semsarian C, Bernstein S, et al. Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia. Proc Natl Acad Sci U S A. 2005;102:18123-8 pubmed..We suggest that a shared pathway triggered by sarcomere gene mutations links cardiac hypertrophy and arrhythmias in HCM. ..
- Franco D, Icardo J. Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts. Cardiovasc Res. 2001;49:417-29 pubmed..The AVB expresses betaMHC and MLC2v, but no alphaMHC, MLC2a, Cx43, desmin or alpha-SMA...
- Niederreither K, Vermot J, Messaddeq N, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Development. 2001;128:1019-31 pubmed..However, cardiac neural crest cells cannot be properly rescued in Raldh2(-/- )embryos, leading to outflow tract septation defects. ..
- Hotta Y, Sasaki S, Konishi M, Kinoshita H, Kuwahara K, Nakao K, et al. Fgf16 is required for cardiomyocyte proliferation in the mouse embryonic heart. Dev Dyn. 2008;237:2947-54 pubmed publisher..The embryonic heart phenotype is similar to that of the Fgf9 knockout heart, indicating Fgf9 and Fgf16 to synergistically act as growth factors for embryonic cardiomyocytes. ..
- Murakami N, Trenkner E, Elzinga M. Changes in expression of nonmuscle myosin heavy chain isoforms during muscle and nonmuscle tissue development. Dev Biol. 1993;157:19-27 pubmed..In cryosections of skeletal and cardiac muscles, MIIB2 was localized within the muscle cells, while MIIA and MIIApla were primarily in the blood vessels and capillaries. ..
- Shirai M, Osugi T, Koga H, Kaji Y, Takimoto E, Komuro I, et al. The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis. J Clin Invest. 2002;110:177-84 pubmed..5 expression in cardiomyocytes. Thus, our data show that a mammalian PcG gene can play a key role in organogenesis by helping to maintain the expression of a selector gene. ..
- Park I, Han C, Jin S, Lee B, Choi H, Kwon J, et al. Myosin regulatory light chains are required to maintain the stability of myosin II and cellular integrity. Biochem J. 2011;434:171-80 pubmed publisher..Taken together, our study provides direct evidence that normal levels of non-muscle RLCs are essential for maintaining the integrity of myosin II, and indicates that the RLCs are critical for cell structure and dynamics. ..
- Wang J, Greene S, Bonilla Claudio M, Tao Y, Zhang J, Bai Y, et al. Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell. 2010;19:903-12 pubmed publisher..Our findings indicate that Bmp signaling directly regulates a miRNA-mediated effector mechanism that downregulates cardiac progenitor genes and enhances myocardial differentiation. ..
- Davis J, Davis L, Correll R, Makarewich C, Schwanekamp J, Moussavi Harami F, et al. A Tension-Based Model Distinguishes Hypertrophic versus Dilated Cardiomyopathy. Cell. 2016;165:1147-1159 pubmed publisher..This tension-based model also has the potential to inform pharmacologic treatment options in cardiomyopathy patients. ..
- Xu C, Liguori G, Persico M, Adamson E. Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes. Development. 1999;126:483-94 pubmed..Therefore, lethality in the absence of Cr1, likely resulted largely from defective precardiac mesoderm that was unable to differentiate into functional cardiomyocytes. ..
- Weydert A, Daubas P, Lazaridis I, Barton P, Garner I, Leader D, et al. Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene. Proc Natl Acad Sci U S A. 1985;82:7183-7 pubmed..This result is in contrast to that for other contractile protein genes such as the alkali myosin light chain and the actin multigene families, which are dispersed in the genome. ..
- Lai L, Leone T, Zechner C, Schaeffer P, Kelly S, Flanagan D, et al. Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 2008;22:1948-61 pubmed publisher..We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. ..
- Fassler R, Rohwedel J, Maltsev V, Bloch W, Lentini S, Guan K, et al. Differentiation and integrity of cardiac muscle cells are impaired in the absence of beta 1 integrin. J Cell Sci. 1996;109 ( Pt 13):2989-99 pubmed..Thus, we conclude that interactions with the extracellular matrix via beta 1 integrin is necessary for differentiation and the maintenance of a specialized phenotype of cardiac muscle cells. ..
- Waller B, McQuinn T, Phelps A, Markwald R, Lo C, Thompson R, et al. Conotruncal anomalies in the trisomy 16 mouse: an immunohistochemical analysis with emphasis on the involvement of the neural crest. Anat Rec. 2000;260:279-93 pubmed..Our observations strongly suggest that abnormal neural crest cell behavior is involved in the pathogenesis of the conotruncal malformations in the Ts16 mouse. ..
- Palmer B, Wang Y, Teekakirikul P, Hinson J, Fatkin D, Strouse S, et al. Myofilament mechanical performance is enhanced by R403Q myosin in mouse myocardium independent of sex. Am J Physiol Heart Circ Physiol. 2008;294:H1939-47 pubmed publisherMale but not female mice carrying a single R403Q missense allele for cardiac alpha-myosin heavy chain (M-alphaMHC(R403Q/+) and F-alphaMHC(R403Q/+), respectively) develop significant hypertrophic cardiomyopathy (HCM) compared with male and ..
- Ya J, Erdtsieck Ernste E, de Boer P, van Kempen M, Jongsma H, Gros D, et al. Heart defects in connexin43-deficient mice. Circ Res. 1998;82:360-6 pubmed
- Schmitt J, Semsarian C, Arad M, Gannon J, Ahmad F, Duffy C, et al. Consequences of pressure overload on sarcomere protein mutation-induced hypertrophic cardiomyopathy. Circulation. 2003;108:1133-8 pubmed..Defining distinct signaling pathways that trigger myocyte growth should help to tailor therapies for cardiac hypertrophy. ..
- Zhang J, Liu J, Huang Y, Chang J, Liu L, McKeehan W, et al. FRS2?-mediated FGF signals suppress premature differentiation of cardiac stem cells through regulating autophagy activity. Circ Res. 2012;110:e29-39 pubmed publisher..The findings provide the first evidence that autophagy plays a role in heart progenitor differentiation. ..
- Dennehey B, Leinwand L, Krauter K. Diversity in transcriptional start site selection and alternative splicing affects the 5'-UTR of mouse striated muscle myosin transcripts. J Muscle Res Cell Motil. 2006;27:559-75 pubmed..The cardiac Myh6 gene had two major TSSs. Use of the major downstream site led to an alternatively spliced second exon...
- Farza H, Watkins H. Animal models of familial hypertrophic cardiomyopathy. Mol Med Today. 1999;5:544-5 pubmed
- Houzelstein D, Lyons G, Chamberlain J, Buckingham M. Localization of dystrophin gene transcripts during mouse embryogenesis. J Cell Biol. 1992;119:811-21 pubmed..The findings are discussed in the context of the pathology of Duchenne muscular dystrophy. ..
- Vikstrom K, Leinwand L. Contractile protein mutations and heart disease. Curr Opin Cell Biol. 1996;8:97-105 pubmed..Biochemical data from studies of mutant myosin suggest a dominant-negative mechanism for inheritance of this disease. The most likely primary defect is sarcomere dysfunction, which is followed by the major clinical symptoms. ..