{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:25:17Z","timestamp":1759742717161,"version":"3.41.2"},"reference-count":115,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"crossref","award":["MDA628561"],"award-info":[{"award-number":["MDA628561"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011347","name":"University of Nevada, Reno","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Laminin-\u03b12-related congenital muscular dystrophy (LAMA2-CMD) is a neuromuscular disease affecting around 1-9 in 1,000,000 children. LAMA2-CMD is caused by mutations in the LAMA2 gene resulting in the loss of laminin-211\/221 heterotrimers in skeletal muscle. LAMA2-CMD patients exhibit severe hypotonia and progressive muscle weakness. Currently, there is no effective treatment for LAMA2-CMD and patients die prematurely. The loss of laminin-\u03b12 results in muscle degeneration, defective muscle repair and dysregulation of multiple signaling pathways. Signaling pathways that regulate muscle metabolism, survival and fibrosis have been shown to be dysregulated in LAMA2-CMD. As vemurafenib is a US Food and Drug Administration (FDA)-approved serine\/threonine kinase inhibitor, we investigated whether vemurafenib could restore some of the serine\/threonine kinase-related signaling pathways and prevent disease progression in the dyW\u2212\/\u2212 mouse model of LAMA2-CMD. Our results show that vemurafenib reduced muscle fibrosis, increased myofiber size and reduced the percentage of fibers with centrally located nuclei in dyW\u2212\/\u2212 mouse hindlimbs. These studies show that treatment with vemurafenib restored the TGF-\u03b2\/SMAD3 and mTORC1\/p70S6K signaling pathways in skeletal muscle. Together, our results indicate that vemurafenib partially improves histopathology but does not improve muscle function in a mouse model of LAMA2-CMD.<\/jats:p>","DOI":"10.1242\/dmm.049916","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T08:51:00Z","timestamp":1680771060000},"source":"Crossref","is-referenced-by-count":6,"title":["Vemurafenib improves muscle histopathology in a mouse model of <i>LAMA2<\/i>-related congenital muscular dystrophy"],"prefix":"10.1242","volume":"16","author":[{"given":"Ariany","family":"Oliveira-Santos","sequence":"first","affiliation":[{"name":"University of Nevada Reno, School of Medicine, Center for Molecular Medicine Department of Pharmacology , , Reno, NV 89557 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisela","family":"Dagda","sequence":"additional","affiliation":[{"name":"University of Nevada Reno, School of Medicine, Center for Molecular Medicine Department of Pharmacology , , Reno, NV 89557 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Wittmann","sequence":"additional","affiliation":[{"name":"University of Nevada Reno, School of Medicine, Center for Molecular Medicine Department of Pharmacology , , Reno, NV 89557 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Smalley","sequence":"additional","affiliation":[{"name":"University of Nevada Reno, School of Medicine, Center for Molecular Medicine Department of Pharmacology , , Reno, NV 89557 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-5258","authenticated-orcid":false,"given":"Dean J.","family":"Burkin","sequence":"additional","affiliation":[{"name":"University of Nevada Reno, School of Medicine, Center for Molecular Medicine Department of Pharmacology , , Reno, NV 89557 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"2023051009534705500_DMM049916C1","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.1093\/hmg\/ddw291","article-title":"IGF-1\/GH axis enhances losartan treatment in Lama2-related muscular dystrophy","volume":"25","author":"Accorsi","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2020.00003","article-title":"Fibrogenesis in LAMA2-related muscular dystrophy is a central tenet of disease etiology","volume":"13","author":"Accorsi","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"2023051009534705500_DMM049916C3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/sj.ejhg.5200743","article-title":"Merosin-deficient congenital muscular dystrophy, autosomal recessive (MDC1A, MIM#156225, LAMA2 gene coding for \u03b12 chain of laminin)","volume":"10","author":"Allamand","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"2023051009534705500_DMM049916C4","doi-asserted-by":"publisher","first-page":"7792","DOI":"10.1038\/s41467-022-35547-0","article-title":"Muscle 4EBP1 activation modifies the structure and function of the neuromuscular junction in mice","volume":"13","author":"Ang","year":"2022","journal-title":"Nat. Commun."},{"key":"2023051009534705500_DMM049916C5","doi-asserted-by":"publisher","first-page":"4914","DOI":"10.1093\/hmg\/ddt341","article-title":"Highly efficient in vivo delivery of PMO into regenerating myotubes and rescue in laminin-\u03b12 chain-null congenital muscular dystrophy mice","volume":"22","author":"Aoki","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C6","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.matbio.2005.05.006","article-title":"A simplified laminin nomenclature","volume":"24","author":"Aumailley","year":"2005","journal-title":"Matrix Biol."},{"key":"2023051009534705500_DMM049916C7","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1093\/hmg\/ddaa104","article-title":"Laminin-111 protein therapy after disease onset slows muscle disease in a mouse model of laminin-\u03b12 related congenital muscular dystrophy","volume":"29","author":"Barraza-Flores","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C9","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1002\/pbc.24891","article-title":"Vemurafenib in pediatric patients with BRAFV600E mutated high-grade gliomas","volume":"61","author":"Bautista","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"2023051009534705500_DMM049916C10","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/ncb1101-1014","article-title":"Akt\/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo","volume":"3","author":"Bodine","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"2023051009534705500_DMM049916C11","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1093\/hmg\/ddq499","article-title":"Proteasome inhibition improves the muscle of laminin \u03b12 chain-deficient mice","volume":"20","author":"Carmignac","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C12","doi-asserted-by":"publisher","first-page":"4891","DOI":"10.1093\/hmg\/ddr427","article-title":"Autophagy is increased in laminin \u03b12 chain-deficient muscle and its inhibition improves muscle morphology in a mouse model of MDC1A","volume":"20","author":"Carmignac","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C13","doi-asserted-by":"publisher","first-page":"76","DOI":"10.4081\/ejtm.2016.5894","article-title":"Severely atrophic human muscle fibers with nuclear misplacement survive many years of permanent denervation","volume":"26","author":"Carraro","year":"2016","journal-title":"Eur. J. Transl. Myol."},{"key":"2023051009534705500_DMM049916C14","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cmet.2013.03.015","article-title":"Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy","volume":"17","author":"Castets","year":"2013","journal-title":"Cell Metab."},{"key":"2023051009534705500_DMM049916C15","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1038\/s41467-017-01236-6","article-title":"Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis","volume":"8","author":"Chakraborty","year":"2017","journal-title":"Nat. Commun."},{"key":"2023051009534705500_DMM049916C16","doi-asserted-by":"publisher","first-page":"847","DOI":"10.3390\/ijms20040847","article-title":"The cutting edge: The role of mTOR signaling in laminopathies","volume":"20","author":"Chiarini","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2023051009534705500_DMM049916C17","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/S0165-5728(02)00104-2","article-title":"Complement 3 deficiency and oral prednisolone improve strength and prolong survival of laminin \u03b12-deficient mice","volume":"127","author":"Connolly","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"2023051009534705500_DMM049916C18","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s12253-017-0324-1","article-title":"Efficacy of Vemurafenib treatment in 43 metastatic melanoma patients with BRAF mutation. Single-institute retrospective analysis, early real-life survival data","volume":"25","author":"Czirbesz","year":"2019","journal-title":"Pathol. Oncol. Res."},{"key":"2023051009534705500_DMM049916C19","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.nmd.2010.02.002","article-title":"Improved muscle strength and mobility in the dy2J\/dy2J mouse with merosin deficient congenital muscular dystrophy treated with Glatiramer acetate","volume":"20","author":"Dadush","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21031092","article-title":"Displaced myonuclei in cancer cachexia suggest altered innervation","volume":"21","author":"Daou","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2023051009534705500_DMM049916C21","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1074\/mcp.M113.032276","article-title":"Quantitative proteomic analysis reveals metabolic alterations, calcium dysregulation, and increased expression of extracellular matrix proteins in laminin \u03b12 chain\u2013deficient muscle","volume":"13","author":"de Oliveira","year":"2014","journal-title":"Mol. Cell. Proteomics"},{"key":"2023051009534705500_DMM049916C22","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1242\/jcs.083311","article-title":"Transgenic overexpression of the \u03b17 integrin reduces muscle pathology and improves viability in the dy(W) mouse model of merosin-deficient congenital muscular dystrophy type 1A","volume":"124","author":"Doe","year":"2011","journal-title":"J. Cell Sci."},{"key":"2023051009534705500_DMM049916C23","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00441-009-0838-2","article-title":"Laminins","volume":"339","author":"Durbeej","year":"2010","journal-title":"Cell Tissue Res."},{"key":"2023051009534705500_DMM049916C24","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/bs.ctm.2015.05.002","article-title":"Laminin-alpha2 chain-deficient congenital muscular dystrophy: pathophysiology and development of treatment","volume":"76","author":"Durbeej","year":"2015","journal-title":"Curr. Top. Membr."},{"key":"2023051009534705500_DMM049916C25","doi-asserted-by":"publisher","first-page":"917","DOI":"10.2119\/molmed.2010.00256","article-title":"Rapamycin ameliorates dystrophic phenotype in mdx mouse skeletal muscle","volume":"17","author":"Eghtesad","year":"2011","journal-title":"Mol. Med."},{"key":"2023051009534705500_DMM049916C26","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1002\/ana.22694","article-title":"Losartan, a therapeutic candidate in congenital muscular dystrophy: studies in the dy2J\/dy2J mouse","volume":"71","author":"Elbaz","year":"2012","journal-title":"Ann. Neurol."},{"key":"2023051009534705500_DMM049916C27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cddis.2015.60","article-title":"Life or death by NF\u03baB, Losartan promotes survival in dy2J\/dy2J mouse of MDC1A","volume":"6","author":"Elbaz","year":"2015","journal-title":"Cell Death Dis."},{"key":"2023051009534705500_DMM049916C28","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1124\/jpet.109.160754","article-title":"Omigapil ameliorates the pathology of muscle dystrophy caused by Laminin-\u03b12 deficiency","volume":"331","author":"Erb","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2023051009534705500_DMM049916C29","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s12185-021-03205-8","article-title":"Vemurafenib provides a rapid and robust clinical response in pediatric Langerhans cell histiocytosis with the BRAF V600E mutation but does not eliminate low-level minimal residual disease per ddPCR using cell-free circulating DNA","volume":"114","author":"Evseev","year":"2021","journal-title":"Int. J. Hematol."},{"key":"2023051009534705500_DMM049916C30","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.1038\/sj.onc.1207542","article-title":"Target of rapamycin (TOR): An integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression","volume":"23","author":"Fingar","year":"2004","journal-title":"Oncogene"},{"key":"2023051009534705500_DMM049916C31","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13395-016-0091-9","article-title":"Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy","volume":"6","author":"Foltz","year":"2016","journal-title":"Skelet. Muscle"},{"key":"2023051009534705500_DMM049916C32","doi-asserted-by":"publisher","first-page":"16302","DOI":"10.1038\/s41598-018-34362-2","article-title":"Effects of metformin on congenital muscular dystrophy type 1A disease progression in mice: a gender impact study","volume":"8","author":"Fontes-Oliveira","year":"2018","journal-title":"Sci. Rep."},{"key":"2023051009534705500_DMM049916C33","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/mus.21616","article-title":"Transgenic overexpression of laminin \u03b11 chain in laminin \u03b12 chain-deficient mice rescues the disease throughout the lifespan","volume":"42","author":"Gawlik","year":"2010","journal-title":"Muscle Nerve"},{"key":"2023051009534705500_DMM049916C34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/2044-5040-1-9","article-title":"Skeletal muscle laminin and MDC1A: pathogenesis and treatment strategies","volume":"1","author":"Gawlik","year":"2011","journal-title":"Skelet. Muscle"},{"key":"2023051009534705500_DMM049916C35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2020.00059","article-title":"A family of Laminin \u03b12 chain-deficient mouse mutants: advancing the research on LAMA2-CMD","volume":"13","author":"Gawlik","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"2023051009534705500_DMM049916C36","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1093\/hmg\/ddh190","article-title":"Laminin \u03b11 chain reduces muscular dystrophy in laminin chain deficient mice","volume":"13","author":"Gawlik","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C37","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.matbio.2018.02.024","article-title":"Laminin \u03b11 reduces muscular dystrophy in dy2J mice","volume":"70","author":"Gawlik","year":"2018","journal-title":"Matrix Biol."},{"key":"2023051009534705500_DMM049916C38","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.nmd.2010.02.001","article-title":"Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations","volume":"20","author":"Geranmayeh","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C39","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1111\/febs.14384","article-title":"Canonical signaling and nuclear activity of mTOR\u2014a teamwork effort to regulate metabolism and cell growth","volume":"285","author":"Gigu\u00e8re","year":"2018","journal-title":"FEBS J."},{"key":"2023051009534705500_DMM049916C40","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/ana.21523","article-title":"Pathology is alleviated by doxycycline in a laminin-\u03b12-null model of congenital muscular dystrophy","volume":"65","author":"Girgenrath","year":"2009","journal-title":"Ann. Neurol."},{"key":"2023051009534705500_DMM049916C41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/path.2697","article-title":"Autophagy: cellular and molecular mechanisms","volume":"221","author":"Glick","year":"2010","journal-title":"J. Pathol."},{"key":"2023051009534705500_DMM049916C42","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1212\/WNL.0000000000001303","article-title":"Prevalence of congenital muscular dystrophy in Italy: a population study","volume":"84","author":"Graziano","year":"2015","journal-title":"Neurology"},{"key":"2023051009534705500_DMM049916C43","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.3390\/ijms19082265","article-title":"STAT3 in skeletal muscle function and disorders","volume":"19","author":"Guadagnin","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2023051009534705500_DMM049916C44","doi-asserted-by":"publisher","first-page":"e0138625","DOI":"10.1371\/journal.pone.0138625","article-title":"mTOR overactivation and compromised autophagy in the pathogenesis of pulmonary fibrosis","volume":"10","author":"Gui","year":"2015","journal-title":"PLoS ONE"},{"key":"2023051009534705500_DMM049916C45","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/s0960-8966(02)00266-3","article-title":"Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice","volume":"13","author":"Guo","year":"2003","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C46","doi-asserted-by":"publisher","first-page":"4463","DOI":"10.1016\/j.febslet.2006.07.015","article-title":"Bone marrow transplantation improves outcome in a mouse model of congenital muscular dystrophy","volume":"580","author":"Hagiwara","year":"2006","journal-title":"FEBS Lett."},{"key":"2023051009534705500_DMM049916C47","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/S0022-510X(98)00084-7","article-title":"Examining potential drug therapies for muscular dystrophy utilising the dy\/dy mouse: I. Clenbuterol","volume":"157","author":"Hayes","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"2023051009534705500_DMM049916C48","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/ng1095-216","article-title":"Mutations in the laminin \u03b12-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy","volume":"11","author":"Helbling-Leclerc","year":"1995","journal-title":"Nat. Genet."},{"key":"2023051009534705500_DMM049916C49","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.nmd.2005.05.004","article-title":"Genetic background influences muscular dystrophy","volume":"15","author":"Heydemann","year":"2005","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C50","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.3390\/ijms20102446","article-title":"Role of transforming growth factor-\u03b2 in skeletal muscle fibrosis: a review","volume":"20","author":"Ismaeel","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2023051009534705500_DMM049916C51","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1136\/jmg.38.10.649","article-title":"The expanding phenotype of laminin \u03b12 chain (merosin) abnormalities: case series and review","volume":"38","author":"Jones","year":"2001","journal-title":"J. Med. Genet."},{"key":"2023051009534705500_DMM049916C52","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/nm.4367","article-title":"Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism","volume":"23","author":"Kemaladewi","year":"2017","journal-title":"Nat. Med."},{"key":"2023051009534705500_DMM049916C53","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/978-981-13-1435-3_10","article-title":"Ubiquitin-proteasome pathway and muscle atrophy","volume":"1088","author":"Khalil","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023051009534705500_DMM049916C54","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s00204-015-1472-2","article-title":"Compromised MAPK signaling in human diseases: an update","volume":"89","author":"Kim","year":"2015","journal-title":"Arch. Toxicol."},{"key":"2023051009534705500_DMM049916C55","doi-asserted-by":"publisher","first-page":"e0146471","DOI":"10.1371\/journal.pone.0146471","article-title":"Bortezomib does not reduce muscular dystrophy in the dy2J\/dy2J mouse model of Laminin \u03b12 chain-deficient muscular dystrophy","volume":"11","author":"K\u00f6rner","year":"2016","journal-title":"PLoS ONE"},{"key":"2023051009534705500_DMM049916C56","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1016\/j.ajpath.2014.01.019","article-title":"Bortezomib partially improves laminin \u03b12 chain deficient muscular dystrophy","volume":"184","author":"K\u00f6rner","year":"2014","journal-title":"Am. J. Pathol."},{"key":"2023051009534705500_DMM049916C57","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1172\/JCI3705","article-title":"Merosin-deficient congenital muscular dystrophy: partial genetic correction in two mouse models","volume":"102","author":"Kuang","year":"1998","journal-title":"J. Clin. Investig."},{"key":"2023051009534705500_DMM049916C58","first-page":"1601","article-title":"Activation of the lama2 gene in muscle regeneration: Abortive regeneration in laminin \u03b12-deficiency","volume":"79","author":"Kuang","year":"1999","journal-title":"Lab. Investig."},{"key":"2023051009534705500_DMM049916C59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fonc.2022.794216","article-title":"Dimethyl fumarate combined with vemurafenib enhances anti-melanoma efficacy via inhibiting the Hippo\/YAP, NRF2-ARE, and AKT\/mTOR\/ERK pathways in A375 melanoma cells","volume":"12","author":"Li","year":"2022","journal-title":"Front. Oncol."},{"key":"2023051009534705500_DMM049916C60","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1158\/1078-0432.CCR-11-2197","article-title":"Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma","volume":"18","author":"Luke","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"2023051009534705500_DMM049916C61","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/S0960-8966(00)00192-9","article-title":"IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice","volume":"11","author":"Lynch","year":"2001","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C62","doi-asserted-by":"publisher","first-page":"622","DOI":"10.15252\/emmm.201607052","article-title":"STAT3 promotes IFN\u03b3\/TNF\u03b1\u2013induced muscle wasting in an NF\u2013\u03baB\u2013dependent and IL\u20136\u2013independent manner","volume":"9","author":"Ma","year":"2017","journal-title":"EMBO Mol Med"},{"key":"2023051009534705500_DMM049916C63","doi-asserted-by":"publisher","first-page":"6615","DOI":"10.1128\/MCB.13.11.6615","article-title":"Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro","volume":"13","author":"Macdonald","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"2023051009534705500_DMM049916C64","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.bbamcr.2006.10.001","article-title":"Roles of the Raf\/MEK\/ERK pathway in cell growth, malignant transformation, and drug resistance","volume":"1773","author":"McCubrey","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"2023051009534705500_DMM049916C65","doi-asserted-by":"publisher","first-page":"8984","DOI":"10.1074\/jbc.M809719200","article-title":"Scaffold-forming and adhesive contributions of synthetic laminin-binding proteins to basement membrane assembly","volume":"284","author":"McKee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2023051009534705500_DMM049916C66","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/2044-5040-4-14","article-title":"Dysregulation of matricellular proteins is an early signature of pathology in laminin-deficientmuscular dystrophy","volume":"4","author":"Mehuron","year":"2014","journal-title":"Skelet. Muscle"},{"key":"2023051009534705500_DMM049916C67","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/2044-5040-2-18","article-title":"Angiotensin II type 1 receptor antagonists alleviate muscle pathology in the mouse model for laminin-\u03b12-deficient congenital muscular dystrophy (MDC1A)","volume":"2","author":"Meinen","year":"2012","journal-title":"Skelet. Muscle"},{"key":"2023051009534705500_DMM049916C68","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S0960-8966(96)00383-5","article-title":"Sequential study of central and peripheral nervous system involvement in an infant with merosin-deficient congenital muscular dystrophy","volume":"6","author":"Mercuri","year":"1996","journal-title":"Neuromuscul. Disroder."},{"key":"2023051009534705500_DMM049916C69","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/nm1736","article-title":"Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy","volume":"14","author":"Millay","year":"2008","journal-title":"Nat. Med."},{"key":"2023051009534705500_DMM049916C70","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0014-5793(97)01007-7","article-title":"Laminin \u03b12 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy","volume":"415","author":"Miyagoe","year":"1997","journal-title":"FEBS Lett."},{"key":"2023051009534705500_DMM049916C71","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/(SICI)1097-0029(20000201\/15)48:3\/4&lt;181::AID-JEMT6&gt;3.0.CO;2-Q","article-title":"Merosin and congenital muscular dystrophy","volume":"48","author":"Miyagoe-Suzuki","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"2023051009534705500_DMM049916C72","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/35095054","article-title":"An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy","volume":"413","author":"Moll","year":"2001","journal-title":"Nature"},{"key":"2023051009534705500_DMM049916C73","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/2044-5040-3-17","article-title":"Inhibition of extracellular signal-regulated kinase 1\/2 signaling has beneficial effects on skeletal muscle in a mouse model of Emery-Dreifuss muscular dystrophy caused by lamin A\/C gene mutation","volume":"3","author":"Muchir","year":"2013","journal-title":"Skelet. Muscle"},{"key":"2023051009534705500_DMM049916C74","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.canlet.2020.07.025","article-title":"JNK signaling contributes to skeletal muscle wasting and protein turnover in pancreatic cancer cachexia","volume":"491","author":"Mulder","year":"2020","journal-title":"Cancer Lett."},{"key":"2023051009534705500_DMM049916C75","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.nmd.2004.06.009","article-title":"The congenital muscular dystrophies in 2004: a century of exciting progress","volume":"14","author":"Muntoni","year":"2004","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C76","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/glia.1075","article-title":"Schwann cell myelination occurred without basal lamina formation in laminin \u03b12 chain-null mutant (dy3K\/dy3K) mice","volume":"35","author":"Nakagawa","year":"2001","journal-title":"Glia"},{"key":"2023051009534705500_DMM049916C77","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1002\/mus.21706","article-title":"Fibrosis inhibition and muscle histopathology improvement in laminin-\u03b12-deficient mice","volume":"42","author":"Nevo","year":"2010","journal-title":"Muscle Nerve"},{"key":"2023051009534705500_DMM049916C78","doi-asserted-by":"publisher","first-page":"e18049","DOI":"10.1371\/journal.pone.0018049","article-title":"The Ras Antagonist, Farnesylthiosalicylic Acid (FTS), decreases fibrosis and improves muscle strength in dy2J\/dy2J mouse model of muscular dystrophy","volume":"6","author":"Nevo","year":"2011","journal-title":"PLoS ONE"},{"key":"2023051009534705500_DMM049916C79","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2147\/TACG.S187481","article-title":"Current understanding and treatment of cardiac and skeletal muscle pathology in laminin-\u03b12 chain-deficient congenital muscular dystrophy","volume":"12","author":"Nguyen","year":"2019","journal-title":"Appl. Clin. Genet."},{"key":"2023051009534705500_DMM049916C80","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1093\/brain\/awp236","article-title":"Prevalence of genetic muscle disease in Northern England: In-depth analysis of a muscle clinic population","volume":"132","author":"Norwood","year":"2009","journal-title":"Brain"},{"key":"2023051009534705500_DMM049916C81","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1093\/hmg\/ddx083","article-title":"Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy","volume":"26","author":"Nunes","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C82","first-page":"1","article-title":"LAMA2 muscular dystrophy","author":"Oliveira","year":"2020","journal-title":"GeneReviews\u00ae [Internet]"},{"key":"2023051009534705500_DMM049916C83","doi-asserted-by":"publisher","first-page":"e55","DOI":"10.7417\/CT.2019.2108","article-title":"The MIG chemokine in inflammatory myopathies","volume":"1","author":"Paparo","year":"2019","journal-title":"Clin. Terapeutica"},{"key":"2023051009534705500_DMM049916C84","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1002\/1097-0029(20001101)51:3&lt;247::AID-JEMT5&gt;3.0.CO;2-Z","article-title":"Laminins of the neuromuscular system","volume":"51","author":"Patton","year":"2000","journal-title":"Microsc. Res. Tech"},{"key":"2023051009534705500_DMM049916C85","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1083\/jcb.139.6.1507","article-title":"Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice","volume":"139","author":"Patton","year":"1997","journal-title":"J. Cell Biol."},{"key":"2023051009534705500_DMM049916C86","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1002\/ana.410400515","article-title":"Congenital muscular dystrophy with primary laminin-A2 (merosin) deficiency presenting as inflammatory myopathy","volume":"40","author":"Pegoraro","year":"1996","journal-title":"Annal. Neurol."},{"key":"2023051009534705500_DMM049916C87","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0013604","article-title":"Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition","volume":"5","author":"Penna","year":"2010","journal-title":"PLoS ONE"},{"key":"2023051009534705500_DMM049916C88","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1002\/pro.2374","article-title":"Molecular basis of MAP kinase regulation","volume":"22","author":"Peti","year":"2013","journal-title":"Protein Sci."},{"key":"2023051009534705500_DMM049916C89","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/0960-8966(94)00069-L","article-title":"Clinical phenotype in congenital muscular dystrophy: correlation with expression of merosin in skeletal muscle","volume":"5","author":"Philpot","year":"1995","journal-title":"Neuromuscul. Disord."},{"key":"2023051009534705500_DMM049916C90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2020.00060","article-title":"LAMA2 neuropathies: human findings and pathomechanisms from mouse models","volume":"13","author":"Previtali","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"2023051009534705500_DMM049916C91","doi-asserted-by":"publisher","first-page":"11999","DOI":"10.1073\/pnas.0502137102","article-title":"Amelioration of laminin-\u03b12-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin","volume":"102","author":"Qiao","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051009534705500_DMM049916C92","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/mus.10544","article-title":"EMG and nerve conduction studies in children with congenital muscular dystrophy","volume":"29","author":"Quijano-Roy","year":"2004","journal-title":"Muscle Nerve"},{"key":"2023051009534705500_DMM049916C93","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/S1357-4310(99)01635-4","article-title":"Eotaxin and eosinophil recruitment: implications for human disease","volume":"6","author":"Rankin","year":"2000","journal-title":"Mol. Med. Today"},{"key":"2023051009534705500_DMM049916C94","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scitranslmed.aal4649","article-title":"Linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy in mice","volume":"9","author":"Reinhard","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"2023051009534705500_DMM049916C95","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1016\/j.ajpath.2011.12.019","article-title":"Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy","volume":"180","author":"Rooney","year":"2012","journal-title":"Musculoskelet. Pathol."},{"key":"2023051009534705500_DMM049916C96","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2020.00123","article-title":"LAMA2-related dystrophies: clinical phenotypes, disease biomarkers, and clinical trial readiness","volume":"13","author":"Sarkozy","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"2023051009534705500_DMM049916C97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"2023051009534705500_DMM049916C98","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3233\/JND-200568","article-title":"Molecular mechanisms of skeletal muscle hypertrophy","volume":"8","author":"Schiaffino","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"2023051009534705500_DMM049916C99","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1462399411002109","article-title":"PI3K\/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis","volume":"14","author":"Schultze","year":"2012","journal-title":"Expert Rev. Mol. Med."},{"key":"2023051009534705500_DMM049916C100","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.semcdb.2016.09.013","article-title":"Fibrosis development in early-onset muscular dystrophies: Mechanisms and translational implications","volume":"64","author":"Serrano","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"2023051009534705500_DMM049916C101","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1177\/088307389501000610","article-title":"Demyelinating peripheral neuropathy in merosin-deficient congenital muscular dystrophy","volume":"10","author":"Shorer","year":"1995","journal-title":"J. Child Neurol."},{"key":"2023051009534705500_DMM049916C102","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/978-1-4939-3810-0_19","article-title":"In vitro assays to determine skeletal muscle physiologic function","volume":"1460","author":"Sperringer","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"2023051009534705500_DMM049916C103","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s11010-020-03834-3","article-title":"Gene therapy: a double-edged sword with great powers","volume":"474","author":"Tang","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"2023051009534705500_DMM049916C104","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scisignal.2004809","article-title":"mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases","volume":"7","author":"Tang","year":"2014","journal-title":"Muscle Biol."},{"key":"2023051009534705500_DMM049916C105","doi-asserted-by":"publisher","first-page":"e12943","DOI":"10.1111\/acel.12943","article-title":"mTORC1 underlies age\u2013related muscle fiber damage and loss by inducing oxidative stress and catabolism","volume":"18","author":"Tang","year":"2019","journal-title":"Aging Cell"},{"key":"2023051009534705500_DMM049916C106","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.bbrc.2005.12.224","article-title":"Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-\u03b12 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?","volume":"342","author":"Taniguchi","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023051009534705500_DMM049916C107","first-page":"157","article-title":"Serum calcium-decreasing factor, caldecrin, ameliorates muscular dystrophy in dy\/dy mice","volume":"25","author":"Tomomura","year":"2011","journal-title":"In Vivo (Brooklyn)"},{"key":"2023051009534705500_DMM049916C108","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.1038\/sj.onc.1210415","article-title":"MAP kinases and the control of nuclear events","volume":"26","author":"Turjanski","year":"2007","journal-title":"Oncogene"},{"key":"2023051009534705500_DMM049916C109","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1093\/hmg\/ddt428","article-title":"Laminin-111 improves muscle repair in a mouse model of merosin-deficient congenital muscular dystrophy","volume":"23","author":"van Ry","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"2023051009534705500_DMM049916C110","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.00969","article-title":"BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling","volume":"2","author":"Vin","year":"2013","journal-title":"eLife"},{"key":"2023051009534705500_DMM049916C111","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1177\/0883073810381924","article-title":"Consensus statement on standard of care for congenital muscular dystrophies Ching","volume":"25","author":"Wang","year":"2010","journal-title":"J. Child Neurol."},{"key":"2023051009534705500_DMM049916C112","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1038\/s41418-018-0063-1","article-title":"Inhibition of the JNK\/MAPK signaling pathway by myogenesis-associated miRNAs is required for skeletal muscle development","volume":"25","author":"Xie","year":"2018","journal-title":"Cell Death Differ."},{"key":"2023051009534705500_DMM049916C113","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/cge.12366","article-title":"Genotype\/phenotype analysis in Chinese laminin-\u03b12 deficient congenital muscular dystrophy patients","volume":"87","author":"Xiong","year":"2015","journal-title":"Clin. Genet."},{"key":"2023051009534705500_DMM049916C114","doi-asserted-by":"publisher","first-page":"e65468","DOI":"10.1371\/journal.pone.0065468","article-title":"Omigapil treatment decreases fibrosis and improves respiratory rate in dy2J mouse model of congenital muscular dystrophy","volume":"8","author":"Yu","year":"2013","journal-title":"PLoS ONE"},{"key":"2023051009534705500_DMM049916C115","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1002\/acn3.51172","article-title":"LAMA2-related muscular dystrophy: natural history of a large pediatric cohort","volume":"7","author":"Zambon","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2023051009534705500_DMM049916C116","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s40262-017-0523-7","article-title":"Clinical Pharmacokinetics of Vemurafenib","volume":"56","author":"Zhang","year":"2017","journal-title":"Clin. Pharmacokinet."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.049916\/2781291\/dmm049916.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.049916\/2837094\/dmm049916.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.049916\/2837094\/dmm049916.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T11:55:34Z","timestamp":1683806134000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/16\/6\/dmm049916\/308880\/Vemurafenib-improves-muscle-histopathology-in-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":115,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.049916","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"type":"print","value":"1754-8403"},{"type":"electronic","value":"1754-8411"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"article-number":"dmm049916"}}