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Gene Review

Myh6  -  myosin, heavy polypeptide 6, cardiac...

Mus musculus

Synonyms: A830009F23Rik, AA517445, MyHC-alpha, Myhc-a, Myhca, ...
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Disease relevance of Myh6


High impact information on Myh6

  • The myhc alpha (334-352) peptide strongly induced myocarditis when administered to A/J mice, which was histologically indistinguishable from that induced by myosin [6].
  • The myhc alpha (334-352) epitope was present in cardiac myosin and not skeletal muscle myosins, providing a biochemical basis for the cardiac specificity of this autoimmune disease [6].
  • One peptide, myhc alpha (325-357) strongly stimulated the Seu.5 T cells, localizing the epitope to this region of the myhc alpha molecule [6].
  • Importantly, the myhc alpha (334-352) epitope was able to bind to I-Ak molecules on the surface of antigen-presenting cells in a stable manner [6].
  • Late deletion of Gata4 by Cre recombinase driven by the alpha myosin heavy chain promoter did not selectively affect RV development or generation of endocardial cushion mesenchyme but did result in marked myocardial thinning with decreased cardiomyocyte proliferation, as well as double-outlet RV [7].

Biological context of Myh6

  • We conclude that 45-MHz echocardiography is an excellent tool for assessing cardiac physiology in neonatal mice and that the concentration of Gln403 alpha cardiac MHC in myocytes influences both cell function and cell viability [8].
  • A mouse model of FHC resulting from a mutation in the alpha-myosin heavy-chain (Arg403Gln) was used to study the electrophysiologic phenotype of this disease [9].
  • We used a transgenic ES cell lineage expressing enhanced green fluorescent protein (EGFP) under the control of the alpha-myosin heavy chain (alpha-MHC) promoter (palphaMHC-EGFP) to investigate the effects of 33 small molecules interfering with several signalling cascades on cardiomyogenesis [10].
  • We developed novel, fluorescent-based, myocardial, cellular transplantation systems in order to study these questions in murine embryos and report the irreversible nature of chamber specification with respect to the downregulation of atrial myosin light chain 2 (MLC-2a) and alpha myosin heavy chain (alpha-MHC) [11].
  • In this study, we have rescued these high expression beta-tropomyosin mice by turning off the alpha-myosin heavy chain promoter, which is driving the beta-tropomyosin transgene [12].

Anatomical context of Myh6

  • The alpha-myosin heavy chain (alpha-MyHC) is the major contractile protein expressed in the myocardium of adult mice [13].
  • We used small-amplitude (0.25%) length-perturbation analysis to examine the mechanical properties of skinned left ventricular papillary muscle strips from mouse hearts bearing the R403Q mutation in the alpha-myosin heavy chain (alphaMHC403/+) [14].
  • This down-regulation of the alpha-myosin heavy chain promoter was accomplished by the administration of 5-propyl-2-thiouracil, which disrupts thyroid hormone synthesis and inhibits promoter activity through thyroid regulatory elements located in the 5'-flanking region of the promoter [12].
  • To determine whether recruitment into the myocardial lineage also takes place in these regions, the spatiotemporal pattern of expression of alpha-Sma and of the myocardial markers sarcoplasmatic reticulum calcium ATPase (Serca2a), alpha-myosin heavy chain (Mhc), and beta-Mhc were examined [15].
  • In vitro, Cre driven by cardiac-specific alpha-myosin heavy chain (alphaMyHC) sequences elicited recombination selectively at loxP sites in purified cardiac myocytes, but not cardiac fibroblasts [16].

Associations of Myh6 with chemical compounds

  • To assess the importance of the intergenic region in directing expression of the alpha-cardiac MHC gene, a fragment containing the 3'-end of the beta-cardiac gene and the 5'-end of the alpha-cardiac gene was linked to a chloramphenicol acetyltransferase gene and used to generate transgenic mice [17].
  • In this study, we used the alpha-myosin heavy chain (alphaMHC) promoter to generate transgenic mice overexpressing angiotensin II type 1 (AT1a) receptor selectively in cardiac myocytes [18].
  • The cardiac-restricted alpha-myosin heavy chain promoter was used to target expression of a mutant TGF-beta(1) cDNA harboring a cysteine-to-serine substitution at amino acid residue 33 [19].
  • This study provides direct evidence that USF, a member of the basic helix-loop-helix leucine zipper family, binds to MLE1, HF-1a, and PRE B sites and suggests that it is a component of protein complexes that may coordinately control the expression of MLC-2v and alpha-myosin heavy-chain genes [20].
  • In the absence of DMSO, dynorphin B triggered GATA-4 and Nkx-2.5 gene expression and led to the appearance of both alpha-myosin heavy chain and myosin light chain-2V transcripts, two markers of cardiac differentiation [21].

Physical interactions of Myh6


Regulatory relationships of Myh6


Other interactions of Myh6

  • Analyses of phospholamban transcript levels relative to alpha-myosin heavy chain (alpha-MHC) revealed a 3-fold higher phospholamban abundance in the ventricle compared with the atrium of the FVB/N murine strain [28].
  • In all the stages of development, the beating cells in the EBs of both groups expressed beta-actinin, myosin light chain isoform 2V, cardiac alpha-myosin heavy chain (alpha-MHC), and cardiac beta-myosin heavy chain (beta-MHC) [29].
  • METHODS AND RESULTS: Postnatal transgenic cardiac-specific overexpression of MLC2v was achieved by use of the alpha-myosin heavy chain promoter [30].
  • This is the first report demonstrating that transcriptional regulatory elements located within the alpha-myosin heavy chain promoter can be manipulated to rescue potentially lethal phenotypes, such as high expression beta-tropomyosin transgenic mice [12].
  • We examined the effect of adhesion signaling including Src and focal adhesion kinase (FAK) on cardiogenesis in mouse ES cells using alpha-myosin heavy chain promoter-driven enhanced green fluorescent protein or luciferase as reporters [31].

Analytical, diagnostic and therapeutic context of Myh6


  1. Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14. Traystman, M.D., Chow, L.H., McManus, B.M., Herskowitz, A., Nesbitt, M.N., Beisel, K.W. Am. J. Pathol. (1991) [Pubmed]
  2. Progression from hypertrophic to dilated cardiomyopathy in mice that express a mutant myosin transgene. Freeman, K., Colon-Rivera, C., Olsson, M.C., Moore, R.L., Weinberger, H.D., Grupp, I.L., Vikstrom, K.L., Iaccarino, G., Koch, W.J., Leinwand, L.A. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  3. Electrophysiological abnormalities and arrhythmias in alpha MHC mutant familial hypertrophic cardiomyopathy mice. Berul, C.I., Christe, M.E., Aronovitz, M.J., Seidman, C.E., Seidman, J.G., Mendelsohn, M.E. J. Clin. Invest. (1997) [Pubmed]
  4. Transgenic mice with cardiac overexpression of alpha1B-adrenergic receptors. In vivo alpha1-adrenergic receptor-mediated regulation of beta-adrenergic signaling. Akhter, S.A., Milano, C.A., Shotwell, K.F., Cho, M.C., Rockman, H.A., Lefkowitz, R.J., Koch, W.J. J. Biol. Chem. (1997) [Pubmed]
  5. gp130 plays a critical role in pressure overload-induced cardiac hypertrophy. Uozumi, H., Hiroi, Y., Zou, Y., Takimoto, E., Toko, H., Niu, P., Shimoyama, M., Yazaki, Y., Nagai, R., Komuro, I. J. Biol. Chem. (2001) [Pubmed]
  6. Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart. Donermeyer, D.L., Beisel, K.W., Allen, P.M., Smith, S.C. J. Exp. Med. (1995) [Pubmed]
  7. Morphogenesis of the right ventricle requires myocardial expression of Gata4. Zeisberg, E.M., Ma, Q., Juraszek, A.L., Moses, K., Schwartz, R.J., Izumo, S., Pu, W.T. J. Clin. Invest. (2005) [Pubmed]
  8. Neonatal cardiomyopathy in mice homozygous for the Arg403Gln mutation in the alpha cardiac myosin heavy chain gene. Fatkin, D., Christe, M.E., Aristizabal, O., McConnell, B.K., Srinivasan, S., Schoen, F.J., Seidman, C.E., Turnbull, D.H., Seidman, J.G. J. Clin. Invest. (1999) [Pubmed]
  9. QT dispersion in alpha-myosin heavy-chain familial hypertrophic cardiomyopathy mice. Bevilacqua, L.M., Maguire, C.T., Seidman, J.G., Seidman, C.E., Berul, C.I. Pediatr. Res. (1999) [Pubmed]
  10. Identification of small signalling molecules promoting cardiac-specific differentiation of mouse embryonic stem cells. Sachinidis, A., Schwengberg, S., Hippler-Altenburg, R., Mariappan, D., Kamisetti, N., Seelig, B., Berkessel, A., Hescheler, J. Cell. Physiol. Biochem. (2006) [Pubmed]
  11. Downregulation of atrial markers during cardiac chamber morphogenesis is irreversible in murine embryos. Gruber, P.J., Kubalak, S.W., Chien, K.R. Development (1998) [Pubmed]
  12. Rescue of high expression beta-tropomyosin transgenic mice by 5-propyl-2-thiouracil. Regulating the alpha-myosin heavy chain promoter. Prabhakar, R., Boivin, G.P., Hoit, B., Wieczorek, D.F. J. Biol. Chem. (1999) [Pubmed]
  13. Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart. Jones, W.K., Grupp, I.L., Doetschman, T., Grupp, G., Osinska, H., Hewett, T.E., Boivin, G., Gulick, J., Ng, W.A., Robbins, J. J. Clin. Invest. (1996) [Pubmed]
  14. Altered crossbridge kinetics in the alphaMHC403/+ mouse model of familial hypertrophic cardiomyopathy. Blanchard, E., Seidman, C., Seidman, J.G., LeWinter, M., Maughan, D. Circ. Res. (1999) [Pubmed]
  15. Recruitment of intra- and extracardiac cells into the myocardial lineage during mouse development. Kruithof, B.P., Van Den Hoff, M.J., Tesink-Taekema, S., Moorman, A.F. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2003) [Pubmed]
  16. Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo. Agah, R., Frenkel, P.A., French, B.A., Michael, L.H., Overbeek, P.A., Schneider, M.D. J. Clin. Invest. (1997) [Pubmed]
  17. Isolation and characterization of the mouse cardiac myosin heavy chain genes. Gulick, J., Subramaniam, A., Neumann, J., Robbins, J. J. Biol. Chem. (1991) [Pubmed]
  18. Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block. Hein, L., Stevens, M.E., Barsh, G.S., Pratt, R.E., Kobilka, B.K., Dzau, V.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  19. Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1) transgene in the heart. Nakajima, H., Nakajima, H.O., Salcher, O., Dittiè, A.S., Dembowsky, K., Jing, S., Field, L.J. Circ. Res. (2000) [Pubmed]
  20. The basic helix-loop-helix protein upstream stimulating factor regulates the cardiac ventricular myosin light-chain 2 gene via independent cis regulatory elements. Navankasattusas, S., Sawadogo, M., van Bilsen, M., Dang, C.V., Chien, K.R. Mol. Cell. Biol. (1994) [Pubmed]
  21. Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells. Ventura, C., Maioli, M. Circ. Res. (2000) [Pubmed]
  22. Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Milano, C.A., Dolber, P.C., Rockman, H.A., Bond, R.A., Venable, M.E., Allen, L.F., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  23. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Sohal, D.S., Nghiem, M., Crackower, M.A., Witt, S.A., Kimball, T.R., Tymitz, K.M., Penninger, J.M., Molkentin, J.D. Circ. Res. (2001) [Pubmed]
  24. Altered function in atrium of transgenic mice overexpressing triadin 1. Kirchhefer, U., Baba, H.A., Kobayashi, Y.M., Jones, L.R., Schmitz, W., Neumann, J. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  25. bcl-2 overexpression promotes myocyte proliferation. Limana, F., Urbanek, K., Chimenti, S., Quaini, F., Leri, A., Kajstura, J., Nadal-Ginard, B., Izumo, S., Anversa, P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  26. Transgenic upregulation of IK1 in the mouse heart leads to multiple abnormalities of cardiac excitability. Li, J., McLerie, M., Lopatin, A.N. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  27. Ectopic expression of tropomyosin promotes myofibrillogenesis in mutant axolotl hearts. Zajdel, R.W., McLean, M.D., Lemanski, S.L., Muthuchamy, M., Wieczorek, D.F., Lemanski, L.F., Dube, D.K. Dev. Dyn. (1998) [Pubmed]
  28. Differential phospholamban gene expression in murine cardiac compartments. Molecular and physiological analyses. Koss, K.L., Ponniah, S., Jones, W.K., Grupp, I.L., Kranias, E.G. Circ. Res. (1995) [Pubmed]
  29. Effect of basic fibroblast growth factor on cardiomyocyte differentiation from mouse embryonic stem cells. Khezri, S., Valojerdi, M.R., Sepehri, H., Baharvand, H. Saudi medical journal (2007) [Pubmed]
  30. Effects of total replacement of atrial myosin light chain-2 with the ventricular isoform in atrial myocytes of transgenic mice. Pawloski-Dahm, C.M., Song, G., Kirkpatrick, D.L., Palermo, J., Gulick, J., Dorn, G.W., Robbins, J., Walsh, R.A. Circulation (1998) [Pubmed]
  31. Focal adhesion kinase signaling regulates cardiogenesis of embryonic stem cells. Hakuno, D., Takahashi, T., Lammerding, J., Lee, R.T. J. Biol. Chem. (2005) [Pubmed]
  32. Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types. Maltsev, V.A., Rohwedel, J., Hescheler, J., Wobus, A.M. Mech. Dev. (1993) [Pubmed]
  33. Generation of a conditional null allele of jumonji. Mysliwiec, M.R., Chen, J., Powers, P.A., Bartley, C.R., Schneider, M.D., Lee, Y. Genesis (2006) [Pubmed]
  34. Quantification and characterization of myosin peptide-specific CD4+ T cells in autoimmune myocarditis. Maier, R., Miller, S., Kurrer, M., Krebs, P., de Giuli, R., Kremer, M., Scandella, E., Ludewig, B. J. Immunol. Methods (2005) [Pubmed]
  35. Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells. Min, J.Y., Yang, Y., Sullivan, M.F., Ke, Q., Converso, K.L., Chen, Y., Morgan, J.P., Xiao, Y.F. J. Thorac. Cardiovasc. Surg. (2003) [Pubmed]
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