Gene Symbol: Myh4
Description: myosin, heavy polypeptide 4, skeletal muscle
Alias: AI506973, MHC2B, MYH-2B, Minimsc, Minmus, MyHC-IIb, Myhsf, myosin-4, myHC-2b, myosin heavy chain 2b, myosin heavy chain 4
Species: mouse
Products:     Myh4

Top Publications

  1. Allen D, Leinwand L. Postnatal myosin heavy chain isoform expression in normal mice and mice null for IIb or IId myosin heavy chains. Dev Biol. 2001;229:383-95 pubmed
    ..of seven sarcomeric MyHCs was analyzed in the hindlimb muscles of wild-type mice and in mice null for the MyHC IIb or IId/x genes at several time points from 1 day of postnatal life (dpn) to 20 dpn...
  2. Harrison B, Bell M, Allen D, Byrnes W, Leinwand L. Skeletal muscle adaptations in response to voluntary wheel running in myosin heavy chain null mice. J Appl Physiol (1985). 2002;92:313-22 pubmed
    ..Although this wheel-running activity is lessened compared with NTG, there is evidence of distinct patterns of muscle adaptation in both null strains. ..
  3. van Rooij E, Quiat D, Johnson B, Sutherland L, Qi X, Richardson J, et al. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell. 2009;17:662-73 pubmed publisher
  4. Weydert A, Barton P, Harris A, Pinset C, Buckingham M. Developmental pattern of mouse skeletal myosin heavy chain gene transcripts in vivo and in vitro. Cell. 1987;49:121-9 pubmed
    ..In vitro, in the absence of the nerve, embryonic, perinatal, and adult IIB MHC mRNAs accumulate. The level of the latter two isomRNAs is influenced by culture conditions. ..
  5. Kurapati R, McKenna C, Lindqvist J, Williams D, Simon M, Leproust E, et al. Myofibrillar myopathy caused by a mutation in the motor domain of mouse MyHC IIb. Hum Mol Genet. 2012;21:1706-24 pubmed publisher
    ..mutation resulting in an L342Q change within the motor domain of the skeletal muscle myosin protein MYH4 (MyHC IIb)...
  6. 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. ..
  7. Weiss A, McDonough D, Wertman B, Acakpo Satchivi L, Montgomery K, Kucherlapati R, et al. Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved. Proc Natl Acad Sci U S A. 1999;96:2958-63 pubmed
  8. Weydert A, Daubas P, Caravatti M, Minty A, Bugaisky G, Cohen A, et al. Sequential accumulation of mRNAs encoding different myosin heavy chain isoforms during skeletal muscle development in vivo detected with a recombinant plasmid identified as coding for an adult fast myosin heavy chain from mouse skeletal muscle. J Biol Chem. 1983;258:13867-74 pubmed
    ..There is thus a rapid transition after birth from fetal to adult skeletal muscle myosin heavy chain mRNA sequences. ..
  9. Hagiwara N, Ma B, Ly A. Slow and fast fiber isoform gene expression is systematically altered in skeletal muscle of the Sox6 mutant, p100H. Dev Dyn. 2005;234:301-11 pubmed
    ..Together with our earlier report, demonstrating early postnatal muscle defects in the Sox6 null-p100H mutant, the present results suggest that Sox6 likely plays an important role in muscle development...

Scientific Experts

More Information


  1. Buchberg A, Brownell E, Nagata S, Jenkins N, Copeland N. A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human. Genetics. 1989;122:153-61 pubmed
  2. Plageman T, Chung M, Lou M, Smith A, Hildebrand J, Wallingford J, et al. Pax6-dependent Shroom3 expression regulates apical constriction during lens placode invagination. Development. 2010;137:405-15 pubmed publisher
    ..This provides a previously missing link between lens-induction pathways and the morphogenesis machinery and partly explains the absence of lens morphogenesis in Pax6-deficient mutants. ..
  3. Bakkar N, Ladner K, Canan B, Liyanarachchi S, Bal N, Pant M, et al. IKK? and alternative NF-?B regulate PGC-1? to promote oxidative muscle metabolism. J Cell Biol. 2012;196:497-511 pubmed publisher
    ..Together, these data provide insight on PGC-1? regulation during skeletal myogenesis and reveal a unique function of alternative NF-?B signaling in promoting an oxidative metabolic phenotype. ..
  4. Ford S, Chandra M. Length-dependent effects on cardiac contractile dynamics are different in cardiac muscle containing ?- or ?-myosin heavy chain. Arch Biochem Biophys. 2013;535:3-13 pubmed publisher
    ..These data suggest a mechanism whereby greater cooperative/allosteric effects impart an enhanced length-sensitivity of XB cycling kinetics in fibers containing the slower cycling ?-MHC...
  5. Allen D, Harrison B, Sartorius C, Byrnes W, Leinwand L. Mutation of the IIB myosin heavy chain gene results in muscle fiber loss and compensatory hypertrophy. Am J Physiol Cell Physiol. 2001;280:C637-45 pubmed
    ..Thus loss of the major MyHC isoform produces fiber loss and fiber pathology reminiscent of muscle disease...
  6. Usami A, Abe S, Ide Y. Myosin heavy chain isoforms of the murine masseter muscle during pre- and post-natal development. Anat Histol Embryol. 2003;32:244-8 pubmed
    ..This suggests that the development of murine masseter muscle is closely associated with facial development. ..
  7. Garland T, Morgan M, Swallow J, Rhodes J, Girard I, Belter J, et al. Evolution of a small-muscle polymorphism in lines of house mice selected for high activity levels. Evolution. 2002;56:1267-75 pubmed
  8. Burniston J, Meek T, Pandey S, Broitman Maduro G, Maduro M, Bronikowski A, et al. Gene expression profiling of gastrocnemius of "minimuscle" mice. Physiol Genomics. 2013;45:228-36 pubmed publisher
    ..Consistent with the known reduction of type IIB fibers in HRmini, Myh4 gene expression was -8.82-fold less (P = 0...
  9. Kelly S, Bell T, Selitsky S, Buus R, Hua K, Weinstock G, et al. A novel intronic single nucleotide polymorphism in the myosin heavy polypeptide 4 gene is responsible for the mini-muscle phenotype characterized by major reduction in hind-limb muscle mass in mice. Genetics. 2013;195:1385-95 pubmed publisher
    ..We phenotypically characterized the population and mapped the Minimsc locus to a 2.6-Mb interval on MMU11, a region containing ?100 known or predicted genes...
  10. Rossi A, Mammucari C, Argentini C, Reggiani C, Schiaffino S. Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles. J Physiol. 2010;588:353-64 pubmed publisher
  11. Stark D, Coffey N, Pancoast H, Arnold L, Walker J, Vallée J, et al. Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation. J Cell Biol. 2015;211:1077-91 pubmed publisher
    ..We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life. ..
  12. Cox R, Weydert A, Barlow D, Buckingham M. Three linked myosin heavy chain genes clustered within 370 kb of each other show independent transcriptional and post-transcriptional regulation during differentiation of a mouse muscle cell line. Dev Biol. 1991;143:36-43 pubmed
    ..Post-transcriptional mechanisms also regulate cytoplasmic RNA accumulation of these MHC genes. ..
  13. Lyons G, Ontell M, Cox R, Sassoon D, Buckingham M. The expression of myosin genes in developing skeletal muscle in the mouse embryo. J Cell Biol. 1990;111:1465-76 pubmed
    ..The data presented are the first detailed study of myosin gene expression at these early stages of skeletal muscle development. ..
  14. Sakakibara I, Santolini M, Ferry A, Hakim V, Maire P. Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype. PLoS Genet. 2014;10:e1004386 pubmed publisher
    ..Functional fast-sarcomeric unit formation is achieved by the coordinate expression of fast MYHs and linc-MYH, under the control of a common Six-bound enhancer. ..
  15. Cohen S, Brault J, Gygi S, Glass D, Valenzuela D, Gartner C, et al. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol. 2009;185:1083-95 pubmed publisher
    ..Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1...
  16. Palmer S, Groves N, Schindeler A, Yeoh T, Biben C, Wang C, et al. The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner. J Cell Biol. 2001;153:985-98 pubmed
  17. Robert B, Barton P, Minty A, Daubas P, Weydert A, Bonhomme F, et al. Investigation of genetic linkage between myosin and actin genes using an interspecific mouse back-cross. Nature. 1985;314:181-3 pubmed
    ..No linkage between these genes was observed. ..
  18. Wooldridge A, Fortner C, Lontay B, Akimoto T, Neppl R, Facemire C, et al. Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle. J Biol Chem. 2008;283:11850-9 pubmed publisher
    ..Our findings suggest roles for SMTNL1 in cGMP/cAMP-mediated adaptations to exercise through mechanisms involving direct modulation of contractile activity. ..
  19. Schleef M, Zuhlke C, Schöffl F, Jockusch H. Subtractive cDNA cloning as a tool to analyse secondary effects of a muscle disease. Characterization of affected genes in the myotonic ADR mouse. Neuromuscul Disord. 1994;4:205-17 pubmed
    ..A cDNA derived from the 1100 nucleotide parvalbumin transcript was cloned and the sequence for the as yet unknown 3' extended trailer, generated by alternative polyadenylation, was determined. ..
  20. Nehrenberg D, Wang S, Hannon R, Garland T, Pomp D. QTL underlying voluntary exercise in mice: interactions with the "mini muscle" locus and sex. J Hered. 2010;101:42-53 pubmed publisher
  21. Solinet S, Vitale M. Isoform B of myosin II heavy chain mediates actomyosin contractility during TNFalpha-induced apoptosis. J Cell Sci. 2008;121:1681-92 pubmed publisher
    ..In conclusion, our results demonstrate that MHCIIB, together with MLC phosphorylation and actin, constitute the actomyosin cytoskeleton that mediates contractility during apoptosis. ..
  22. Shi H, Scheffler J, Pleitner J, Zeng C, Park S, Hannon K, et al. Modulation of skeletal muscle fiber type by mitogen-activated protein kinase signaling. FASEB J. 2008;22:2990-3000 pubmed publisher
    ..These data suggest that the MAPK signaling, most likely the ERK1/2 pathway, is necessary to preserve the fast-twitch fiber phenotype with a concomitant repression of slow-twitch fiber program. ..
  23. Issa L, Palmer S, Guven K, Santucci N, Hodgson V, Popovic K, et al. MusTRD can regulate postnatal fiber-specific expression. Dev Biol. 2006;293:104-15 pubmed
    ..These data are consistent with our initial predictions for hMusTRD1alpha1 and suggest that slow fiber genes contain a specific common regulatory element that can be targeted by MusTRD proteins. ..
  24. Kardon G, Harfe B, Tabin C. A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb muscle patterning. Dev Cell. 2003;5:937-44 pubmed
    ..We propose that Tcf4-expressing cells establish a prepattern in the limb mesoderm that determines the sites of myogenic differentiation and thus establishes the basic pattern of limb muscles. ..
  25. Daou N, Lecolle S, Lefebvre S, Della Gaspera B, Charbonnier F, Chanoine C, et al. A new role for the calcineurin/NFAT pathway in neonatal myosin heavy chain expression via the NFATc2/MyoD complex during mouse myogenesis. Development. 2013;140:4914-25 pubmed publisher
    ..Altogether, our findings demonstrate that the calcineurin/NFAT pathway plays a new role in establishing the early muscle fiber type in immature myofibers during embryogenesis. ..
  26. Cho Y, Chema D, Moskow J, Cho M, Schroeder W, Overbeek P, et al. Epidermal surface antigen (MS17S1) is highly conserved between mouse and human. Genomics. 1995;27:251-8 pubmed
    ..These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene. ..
  27. Zhou H, Wan B, Grubisic I, Kaplan T, Tjian R. TAF7L modulates brown adipose tissue formation. elife. 2014;3: pubmed publisher
    ..Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification. ..
  28. Lee Y, Lee S. Regulation of GDF-11 and myostatin activity by GASP-1 and GASP-2. Proc Natl Acad Sci U S A. 2013;110:E3713-22 pubmed publisher
    ..All of these findings suggest that both GASP-1 and GASP-2 are important modulators of GDF-11 and MSTN activity in vivo. ..
  29. Bryce N, Schevzov G, Ferguson V, Percival J, Lin J, Matsumura F, et al. Specification of actin filament function and molecular composition by tropomyosin isoforms. Mol Biol Cell. 2003;14:1002-16 pubmed
    ..We conclude that Tm isoforms can be used to specify the functional properties and molecular composition of actin filaments and that spatial segregation of isoforms may lead to localized specialization of actin filament function. ..
  30. Salamon M, Millino C, Raffaello A, Mongillo M, Sandri C, Bean C, et al. Human MYO18B, a novel unconventional myosin heavy chain expressed in striated muscles moves into the myonuclei upon differentiation. J Mol Biol. 2003;326:137-49 pubmed
    ..In some cases, cardiomyocytes show a partial sarcomeric pattern of MYO18B alternating that of alpha-actinin-2. In skeletal muscle the cytoplasmic MYO18B results much more evident in the fast type fibers. ..
  31. Merrick D, Ting T, Stadler L, Smith J. A role for Insulin-like growth factor 2 in specification of the fast skeletal muscle fibre. BMC Dev Biol. 2007;7:65 pubmed
    ..5-P1). Since specific loss of FMyHC fibres is associated with many skeletal muscle pathologies these data have important medical implications. ..
  32. Gao Y, Chen X, Wang P, Lu L, Zhao W, Chen C, et al. Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance. Proc Natl Acad Sci U S A. 2015;112:13627-32 pubmed publisher
    ..Our results suggest that maternal expression of the imprinted miR-379/miR-544 cluster regulates paternal expression of the Dlk1 gene in mice. We therefore propose a miR-based molecular working model for polar overdominance inheritance. ..
  33. Ontell M, Sopper M, Lyons G, Buckingham M, Ontell M. Modulation of contractile protein gene expression in fetal murine crural muscles: emergence of muscle diversity. Dev Dyn. 1993;198:203-13 pubmed
    ..abstract truncated at 400 words) ..
  34. Sigoillot S, Bourgeois F, Karmouch J, Molgó J, Dobbertin A, Chevalier C, et al. Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ-deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency. FASEB J. 2016;30:2382-99 pubmed publisher
    ..Chevalier, C., Houlgatte, R., Léger, J., Legay, C. Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ-deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency. ..
  35. Lindqvist J, Iwamoto H, Blanco G, Ochala J. The fraction of strongly bound cross-bridges is increased in mice that carry the myopathy-linked myosin heavy chain mutation MYH4L342Q. Dis Model Mech. 2013;6:834-40 pubmed publisher
    ..Here, we have undertaken a detailed functional study of muscle fibers from Myh4(arl) mice, which carry a mutation that provokes an L342Q change within the catalytic domain of the type IIb ..
  36. Suter U, Moskow J, Welcher A, Snipes G, Kosaras B, Sidman R, et al. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci U S A. 1992;89:4382-6 pubmed
    ..Our results strengthen the hypothesis that mutations in the Pmp-22 gene can lead to heterogeneous forms of peripheral neuropathies and offer clues toward possible explanations for the dominant inheritance of these disorders. ..
  37. Lucas M, Goblet C, Keller A, Lamande N, Gros F, Whalen R, et al. Modulation of embryonic and muscle-specific enolase gene products in the developing mouse hindlimb. Differentiation. 1992;51:1-7 pubmed
    ..Quantitative immunoblotting analyses carried out in parallel show that the enolase isozymic transition is mainly controlled at the mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)..
  38. Smith T, Miller J. Distinct myogenic programs of embryonic and fetal mouse muscle cells: expression of the perinatal myosin heavy chain isoform in vitro. Dev Biol. 1992;149:16-26 pubmed
    ..Thus, the myogenic program of fetal, but not embryonic, mouse myogenic cells includes expression of the perinatal MHC isoform upon differentiation in culture. ..
  39. Vivian J, Gan L, Olson E, Klein W. A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation. Dev Biol. 1999;208:44-55 pubmed
  40. Lu B, Allen D, Leinwand L, Lyons G. Spatial and temporal changes in myosin heavy chain gene expression in skeletal muscle development. Dev Biol. 1999;216:312-26 pubmed
    ..The changes in MyHC RNA and protein expression are distinct in different muscles and are restricted in some cases to particular regions of the muscle and do not always reflect their distribution in the adult. ..
  41. 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
    ..and their spatial-temporal expression largely mirrored that of the major transcripts in wild-type, Myh1 null, Myh4 null, injured, and uninjured muscle, except that one form of Myh7, detected in heart, was not detected in diaphragm,..
  42. Sun T, Jayatilake D, Afink G, Ataliotis P, Nister M, Richardson W, et al. A human YAC transgene rescues craniofacial and neural tube development in PDGFRalpha knockout mice and uncovers a role for PDGFRalpha in prenatal lung growth. Development. 2000;127:4519-29 pubmed
    ..In addition, we found that the YAC transgene did not prolong survival of Patch mutant mice, indicating that genetic defects outside the PDGFRalpha locus contribute to the early embryonic lethality of Patch mice. ..
  43. Oh M, Rybkin I, Copeland V, Czubryt M, Shelton J, van Rooij E, et al. Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers. Mol Cell Biol. 2005;25:6629-38 pubmed
    ..These results demonstrate that developmental patterning of slow fibers is independent of calcineurin, while the maintenance of the slow-fiber phenotype in the adult requires calcineurin activity...
  44. Siles L, Sánchez Tilló E, Lim J, Darling D, Kroll K, Postigo A. ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation via CtBP-mediated transcriptional repression. Mol Cell Biol. 2013;33:1368-82 pubmed publisher
    ..These results set ZEB1 as an important regulator of the temporal pattern of gene expression controlling muscle differentiation. ..
  45. Rouger K, Le Cunff M, Steenman M, Potier M, Gibelin N, Dechesne C, et al. Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice. Am J Physiol Cell Physiol. 2002;283:C773-84 pubmed
    ..This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays. ..
  46. Ontell M, Ontell M, Sopper M, Mallonga R, Lyons G, Buckingham M. Contractile protein gene expression in primary myotubes of embryonic mouse hindlimb muscles. Development. 1993;117:1435-44 pubmed
    ..These differences indicate that there is no single coordinate pattern of expression of contractile protein genes during initial formation of the muscles of the mouse.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  47. Petchey L, Risebro C, Vieira J, Roberts T, Bryson J, Greensmith L, et al. Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. Proc Natl Acad Sci U S A. 2014;111:9515-20 pubmed publisher
    ..Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease. ..
  48. Lee K, Singh M, Ussar S, Wetzel P, Hirshman M, Goodyear L, et al. Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism. Nat Commun. 2015;6:8054 pubmed publisher
    ..Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism. ..
  49. Zhang W, Behringer R, Olson E. Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies. Genes Dev. 1995;9:1388-99 pubmed
    ..These results demonstrate an unanticipated regulatory relationship between myogenin and MRF4 and suggest that MRF4 influences rib outgrowth through an indirect mechanism. ..
  50. Agbulut O, Noirez P, Butler Browne G, Jockusch H. Specific isomyosin proportions in hyperexcitable and physiologically denervated mouse muscle. FEBS Lett. 2004;561:191-4 pubmed
    ..In myotonic fast muscles, hyperexcitability leads to a drastic reduction of MyHC IIB which is compensated by IIA. Slow muscles, like soleus and diaphragm, were only marginally changed by myotonia...
  51. Acakpo Satchivi L, Edelmann W, Sartorius C, Lu B, Wahr P, Watkins S, et al. Growth and muscle defects in mice lacking adult myosin heavy chain genes. J Cell Biol. 1997;139:1219-29 pubmed
    ..Many of the phenotypes demonstrated by these mice are typical in human muscle disease and should provide insight into their etiology. ..
  52. Otto A, Macharia R, Matsakas A, Valasek P, Mankoo B, Patel K. A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity. Dev Biol. 2010;343:51-62 pubmed publisher
    ..In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type. ..