{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:58:44Z","timestamp":1790513924824,"version":"4.1.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000894","name":"Spinal Muscular Atrophy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0166803","type":"journal-article","created":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T14:28:47Z","timestamp":1479738527000},"page":"e0166803","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":39,"title":["Activin Receptor Type IIB Inhibition Improves Muscle Phenotype and Function in a Mouse Model of Spinal Muscular Atrophy"],"prefix":"10.1371","volume":"11","author":[{"given":"Min","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Hammers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth R.","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Lee","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,11,21]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ejhg.2011.134","article-title":"Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of &gt;72,400 specimens","volume":"20","author":"EA Sugarman","year":"2011","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"ref2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"S Lefebvre","year":"1995","journal-title":"Cell"},{"issue":"6","key":"ref3","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1086\/515465","article-title":"Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number","volume":"60","author":"PE McAndrew","year":"1997","journal-title":"Am J Hum Genet"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/sj.ejhg.5201288","article-title":"New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations","volume":"12","author":"S Ogino","year":"2004","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.nmd.2008.10.004","article-title":"Ramblings in the history of spinal muscular atrophy","volume":"19","author":"V Dubowitz","year":"2009","journal-title":"Neuromuscul Disord"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/2044-5040-3-24","article-title":"Early onset muscle weakness and disruption of muscle proteins in mouse models of spinal muscular atrophy","volume":"3","author":"JG Boyer","year":"2013","journal-title":"Skelet Muscle"},{"issue":"18","key":"ref7","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1093\/hmg\/ddu189","article-title":"Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics","volume":"23","author":"KV Bricceno","year":"2014","journal-title":"Hum Mol Genet"},{"issue":"10","key":"ref8","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/labinvest.3700163","article-title":"Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients","volume":"84","author":"AS Arnold","year":"2004","journal-title":"Lab Invest"},{"issue":"14","key":"ref9","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.febslet.2012.02.043","article-title":"Promiscuity and specificity in BMP receptor activation","volume":"586","author":"TD Mueller","year":"2012","journal-title":"FEBS Lett"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.tig.2007.08.008","article-title":"Sprinting without myostatin: a genetic determinant of athletic prowess","volume":"23","author":"SJ Lee","year":"2007","journal-title":"Trends Genet"},{"issue":"26","key":"ref11","doi-asserted-by":"crossref","first-page":"15842","DOI":"10.1073\/pnas.2534946100","article-title":"Activation of latent myostatin by the BMP-1\/tolloid family of metalloproteinases","volume":"100","author":"NM Wolfman","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev.cellbio.20.012103.135836","article-title":"Regulation of muscle mass by myostatin","volume":"20","author":"SJ Lee","year":"2004","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1096\/fj.13-245894","article-title":"Elevated expression of activins promotes muscle wasting and cachexia","volume":"28","author":"JL Chen","year":"2014","journal-title":"Faseb J"},{"issue":"1","key":"ref14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.cmet.2015.05.010","article-title":"GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration","volume":"22","author":"MA Egerman","year":"2015","journal-title":"Cell Metab"},{"issue":"6","key":"ref15","doi-asserted-by":"crossref","first-page":"C1258","DOI":"10.1152\/ajpcell.00105.2009","article-title":"Myostatin reduces Akt\/TORC1\/p70S6K signaling, inhibiting myoblast differentiation and myotube size","volume":"296","author":"AU Trendelenburg","year":"2009","journal-title":"Am J Physiol Cell Physiol"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/71709","article-title":"A mouse model for spinal muscular atrophy","volume":"24","author":"HM Hsieh-Li","year":"2000","journal-title":"Nat Genet"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/hmg\/9.3.333","article-title":"The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-\/-) mice and results in a mouse with spinal muscular atrophy","volume":"9","author":"UR Monani","year":"2000","journal-title":"Hum Mol Genet"},{"issue":"6","key":"ref18","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/hmg\/ddi078","article-title":"SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN","volume":"14","author":"TT Le","year":"2005","journal-title":"Hum Mol Genet"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ydbio.2011.05.667","article-title":"Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons","volume":"356","author":"YI Lee","year":"2011","journal-title":"Dev Biol"},{"issue":"17","key":"ref20","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1093\/hmg\/ddp253","article-title":"Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice","volume":"18","author":"CJ Sumner","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.nmd.2011.10.012","article-title":"Transgenic inactivation of murine myostatin does not decrease the severity of disease in a model of Spinal Muscular Atrophy","volume":"22","author":"H Rindt","year":"2012","journal-title":"Neuromuscul Disord"},{"issue":"20","key":"ref22","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1093\/hmg\/dds285","article-title":"Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models","volume":"21","author":"M Osborne","year":"2012","journal-title":"Hum Mol Genet"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"e111428","DOI":"10.1371\/journal.pone.0111428","article-title":"A comparison of three electrophysiological methods for the assessment of disease status in a mild spinal muscular atrophy mouse model","volume":"9","author":"J Li","year":"2014","journal-title":"PLoS One"},{"issue":"5","key":"ref24","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/mus.21743","article-title":"Activin IIB receptor blockade attenuates dystrophic pathology in a mouse model of Duchenne muscular dystrophy","volume":"42","author":"KJ Morine","year":"2010","journal-title":"Muscle Nerve"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"e9176","DOI":"10.1371\/journal.pone.0009176","article-title":"Systemic myostatin inhibition via liver-targeted gene transfer in normal and dystrophic mice","volume":"5","author":"KJ Morine","year":"2010","journal-title":"PLoS One"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ydbio.2012.05.037","article-title":"A cell-autonomous defect in skeletal muscle satellite cells expressing low levels of survival of motor neuron protein","volume":"368","author":"M Hayhurst","year":"2012","journal-title":"Dev Biol"},{"issue":"16","key":"ref27","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1093\/hmg\/ddu142","article-title":"Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy","volume":"23","author":"JG Boyer","year":"2014","journal-title":"Hum Mol Genet"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.yexcr.2005.08.019","article-title":"Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology","volume":"311","author":"D Shafey","year":"2005","journal-title":"Exp Cell Res"},{"issue":"65","key":"ref29","first-page":"291","article-title":"Progress and promise: the current status of spinal muscular atrophy therapeutics","volume":"12","author":"JP Van Meerbeke","year":"2011","journal-title":"Discov Med"},{"issue":"18","key":"ref30","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1073\/pnas.94.18.9920","article-title":"Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos","volume":"94","author":"B Schrank","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"ref31","doi-asserted-by":"crossref","first-page":"e24189","DOI":"10.1371\/journal.pone.0024189","article-title":"Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1(G93A) mouse model of ALS and is harmful in female mice","volume":"6","author":"HM Kaneb","year":"2011","journal-title":"PLoS One"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.clinph.2012.01.028","article-title":"The relationship between Bayesian motor unit number estimation and histological measurements of motor neurons in wild-type and SOD1(G93A) mice","volume":"123","author":"ST Ngo","year":"2012","journal-title":"Clin Neurophysiol"},{"issue":"8","key":"ref33","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1177\/0883073809332702","article-title":"Clinical outcome measures in spinal muscular atrophy","volume":"24","author":"J Montes","year":"2009","journal-title":"J Child Neurol"},{"issue":"6","key":"ref34","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nrneurol.2015.77","article-title":"Spinal muscular atrophy\u2014recent therapeutic advances for an old challenge","volume":"11","author":"I Faravelli","year":"2015","journal-title":"Nat Rev Neurol"},{"issue":"8","key":"ref35","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/0883073807305788","article-title":"Consensus statement for standard of care in spinal muscular atrophy","volume":"22","author":"CH Wang","year":"2007","journal-title":"J Child Neurol"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/mus.10110","article-title":"Spinal muscular atrophy: recent advances and future prospects","volume":"26","author":"S Nicole","year":"2002","journal-title":"Muscle Nerve"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4236\/ojmip.2012.24018","article-title":"Growth and differentiation factor-11 is developmentally regulated in skeletal muscle and inhibits myoblast differentiation","volume":"2","author":"F Jeanplong","year":"2012","journal-title":"Open Journal of Molecular and Integrative Physiology"},{"issue":"50","key":"ref38","doi-asserted-by":"crossref","first-page":"18117","DOI":"10.1073\/pnas.0505996102","article-title":"Regulation of muscle growth by multiple ligands signaling through activin type II receptors","volume":"102","author":"SJ Lee","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.expneurol.2009.02.017","article-title":"A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis","volume":"217","author":"BM Morrison","year":"2009","journal-title":"Exp Neurol"},{"issue":"11","key":"ref40","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1172\/JCI28520","article-title":"Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition","volume":"116","author":"Y Ohsawa","year":"2006","journal-title":"J Clin Invest"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"E157","DOI":"10.1152\/ajpendo.00193.2009","article-title":"Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin","volume":"297","author":"H Gilson","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"12","key":"ref42","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1210\/me.2008-0290","article-title":"Proteomic identification and functional validation of activins and bone morphogenetic protein 11 as candidate novel muscle mass regulators","volume":"22","author":"TA Souza","year":"2008","journal-title":"Mol Endocrinol"},{"issue":"8","key":"ref43","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/mt.2014.90","article-title":"Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy","volume":"22","author":"K Relizani","year":"2014","journal-title":"Mol Ther"},{"issue":"6628","key":"ref44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/387083a0","article-title":"Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member","volume":"387","author":"AC McPherron","year":"1997","journal-title":"Nature"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0006-291X(02)00209-7","article-title":"A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle","volume":"293","author":"M Nishi","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"ref46","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S0006-291X(02)02953-4","article-title":"Inhibition of myostatin in adult mice increases skeletal muscle mass and strength","volume":"300","author":"LA Whittemore","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"issue":"16","key":"ref47","doi-asserted-by":"crossref","first-page":"9306","DOI":"10.1073\/pnas.151270098","article-title":"Regulation of myostatin activity and muscle growth","volume":"98","author":"SJ Lee","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s13311-015-0337-y","article-title":"Spinal Muscular Atrophy Therapeutics: Where do we Stand?","volume":"12","author":"C d'Ydewalle","year":"2015","journal-title":"Neurotherapeutics"},{"issue":"3","key":"ref49","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1152\/japplphysiol.00126.2006","article-title":"Contractile properties of EDL and soleus muscles of myostatin-deficient mice","volume":"101","author":"CL Mendias","year":"2006","journal-title":"J Appl Physiol"},{"issue":"12","key":"ref50","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1089\/hum.2011.102","article-title":"Long-term systemic myostatin inhibition via liver-targeted gene transfer in golden retriever muscular dystrophy","volume":"22","author":"LT Bish","year":"2011","journal-title":"Hum Gene Ther"},{"issue":"3","key":"ref51","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1096\/fj.11-192195","article-title":"Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level?","volume":"26","author":"R Qaisar","year":"2012","journal-title":"FASEB J"},{"issue":"1","key":"ref52","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1083\/jcb.200108071","article-title":"Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice","volume":"157","author":"ER Barton","year":"2002","journal-title":"J Cell Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0166803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T04:55:46Z","timestamp":1540270546000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0166803"}},"subtitle":[],"editor":[{"given":"Ravindra N","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,11,21]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2016,11,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0166803","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,21]]}}}