{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:09:42Z","timestamp":1791284982934,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the dynamin-2 gene (<jats:italic>DNM2<\/jats:italic>) cause autosomal dominant centronuclear myopathy (CNM) and dominant intermediate Charcot-Marie-Tooth (CMT) neuropathy type B (CMTDIB). As the relation between these <jats:italic>DNM2<\/jats:italic>-related diseases is poorly understood, we used zebrafish to investigate the effects of two different <jats:italic>DNM2<\/jats:italic> mutations. First we identified a new alternatively spliced zebrafish <jats:italic>dynamin-2a<\/jats:italic> mRNA (<jats:italic>dnm2a<\/jats:italic>-v2) with greater similarity to human <jats:italic>DNM2<\/jats:italic> than the deposited sequence. Then we knocked-down the zebrafish <jats:italic>dnm2a<\/jats:italic>, producing defects in muscle morphology. Finally, we expressed two mutated <jats:italic>DNM2<\/jats:italic> mRNA by injecting zebrafish embryos with human mRNAs carrying the R522H mutation, causing CNM, or the G537C mutation, causing CMT. Defects arose especially in secondary motor neuron formation, with incorrect branching in embryos injected with CNM-mutated mRNA and total absence of branching in those injected with CMT-mutated mRNA. Muscle morphology in embryos injected with CMT-mutated mRNA appeared less regularly organized than in those injected with CNM-mutated mRNA. Our results showing, a continuum between CNM and CMTDIB phenotypes in zebrafish, similarly to the human conditions, confirm this animal model to be a powerful tool to investigate mutations of <jats:italic>DNM2 in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/srep20466","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T11:23:54Z","timestamp":1454585034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Zebrafish as a Model to Investigate Dynamin 2-Related Diseases"],"prefix":"10.1038","volume":"6","author":[{"given":"Cinzia","family":"Bragato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germano","family":"Gaudenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Blasevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Pavesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Giunta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Cotelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,4]]},"reference":[{"key":"BFsrep20466_CR1","unstructured":"Dyck, P. J., Lebo, R. & Carney, J. A. Hereditary motor and sensory neuropathies. Peripheral neuropathy 3rd edn (eds Poduslo, J. F. et al. ) 1094\u20131136 (Saunders, 1993)."},{"key":"BFsrep20466_CR2","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1001\/archneur.57.5.669","volume":"57","author":"M Nagamatsu","year":"2000","unstructured":"Nagamatsu, M., Jenkins, R. B., Shaid, D. J., Klein, D. M. & Dyck, P. J. Hereditary Motor and Sensory Neuropathy Type 2C is genetically distinct from types 2B and 2D. Arch. Neurol. 57, 669\u2013672 (2000).","journal-title":"Arch. Neurol."},{"key":"BFsrep20466_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10048-002-0130-z","volume":"4","author":"P Berger","year":"2002","unstructured":"Berger, P., Young, P. & Suter, U. Molecular cell Biology of Charcot-Marie-Tooth disease. Neurogen. 4, 1\u201315 (2002).","journal-title":"Neurogen"},{"key":"BFsrep20466_CR4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/ng1514","volume":"37","author":"S Z\u00fcchner","year":"2005","unstructured":"Z\u00fcchner, S. et al. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Nat. Genet. 37, 289\u2013294 (2005).","journal-title":"Nat. Genet."},{"key":"BFsrep20466_CR5","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrm1313","volume":"5","author":"GJK Praefcke","year":"2004","unstructured":"Praefcke, G. J. K. & McMahon, H. T. The dynamin superfamily: universal membrane tubulation and fission molecules? Nat. Rev. | mol. cell. bio. 5, 133\u2013147 (2004).","journal-title":"Nat. Rev. | mol. cell. bio"},{"key":"BFsrep20466_CR6","doi-asserted-by":"publisher","first-page":"4417","DOI":"10.1093\/hmg\/ddt292","volume":"22","author":"E Tinelli","year":"2013","unstructured":"Tinelli, E., Pereira, J. A. & Suter, U. Muscle-specific function of the centronuclear myopathy and Charcot\u2013Marie\u2013Tooth neuropathyassociated dynamin 2 is required for proper lipid metabolism, mitochondria, muscle fibers, neuromuscular junctions and peripheral nerves. Hum. Mol. Genet. 22, 4417\u20134429 (2013).","journal-title":"Hum. Mol. Genet."},{"key":"BFsrep20466_CR7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1006\/jmbi.1996.0002","volume":"255","author":"J Zheng","year":"1996","unstructured":"Zheng, J. et al. Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity. J. Mol. Biol. 255, 14\u201321 (1996).","journal-title":"J. Mol. Biol."},{"key":"BFsrep20466_CR8","first-page":"183","volume":"66","author":"K Tanabe","year":"2012","unstructured":"Tanabe, K. & Takei, K. Dynamin 2 in Charcot-Marie-Tooth Disease. Acta Med. Okayama. 66, 183\u2013190 (2012).","journal-title":"Acta Med. Okayama."},{"key":"BFsrep20466_CR9","doi-asserted-by":"crossref","unstructured":"Jungbluth, H. & Gautel, M. Pathogenic mechanisms in centronuclear myopathies. Front Aging Neurosci. 6, doi: 10.3389\/fnagi.2014.00339 (2014).","DOI":"10.3389\/fnagi.2014.00339"},{"key":"BFsrep20466_CR10","first-page":"1","volume":"8","author":"EM Gibbs","year":"2013","unstructured":"Gibbs, E. M. et al. Two Dynamin-2 Genes Are Required for Normal Zebrafish Development. Plos One. 8, 1\u201310 (2013).","journal-title":"Plos One."},{"key":"BFsrep20466_CR11","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1002\/dvdy.10390","volume":"8","author":"F Pelegri","year":"2003","unstructured":"Pelegri, F. Maternal factors in zebrafish development. Dev. Dyn. 8, 535\u2013554 (2003).","journal-title":"Dev. Dyn."},{"key":"BFsrep20466_CR12","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1242\/dev.033183","volume":"136","author":"W Tadros","year":"2009","unstructured":"Tadros, W. & Lipshitz, H. D. The maternal-to-zygotic transition: a play in two acts. Development. 136, 3033\u20133042 (2009).","journal-title":"Development."},{"key":"BFsrep20466_CR13","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1002\/j.1460-2075.1995.tb07101.x","volume":"14","author":"T Braun","year":"1995","unstructured":"Braun, T. & Arnold, H. Inactivation of Myf-6 and Myf-5 genes in mice leads to alterations in skeletal muscle development. EMBO J. 14, 1176\u20131186 (1995).","journal-title":"EMBO J."},{"key":"BFsrep20466_CR14","first-page":"359","volume":"290","author":"H Lee","year":"2006","unstructured":"Lee, H., Huang, H., Lin, C., Chen, Y. & Tsai, H. Foxd3 mediates zebrafish myf5 expression during early somitogenesis. Development. 290, 359\u2013372 (2006).","journal-title":"Development."},{"key":"BFsrep20466_CR15","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1242\/dev.122.11.3371","volume":"122","author":"SH Devoto","year":"1996","unstructured":"Devoto, S. H., Melan\u00e7on, E., Eisen, J. S. & Westerfield, M. Identification of separate slow and fast muscle precursor cells in vivo, prior to somite formation. Development. 122, 3371\u20133380 (1996).","journal-title":"Development."},{"key":"BFsrep20466_CR16","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1242\/dev.076315","volume":"140","author":"A Pistocchi","year":"2013","unstructured":"Pistocchi, A. et al. Conserved and divergent functions of Nfix in skeletal muscle development during vertebrate evolution. Development. 140, 1528\u20131536 (2013).","journal-title":"Development."},{"key":"BFsrep20466_CR17","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1242\/dev.015719","volume":"135","author":"S Elworthy","year":"2008","unstructured":"Elworthy, S., Hargrave, M., Knight, R., Mebus, K. & Ingham, P. W. Expression of multiple slow myosin heavy chain genes reveals a diversity of zebrafish slow twitch muscle fibers with differing requirements for Hedgehog and Prdm1 activity. Development. 135, 2115\u20132126 (2008).","journal-title":"Development."},{"key":"BFsrep20466_CR18","first-page":"e50925","volume":"82","author":"LL Smith","year":"2013","unstructured":"Smith, L. L., Beggs, A. H. & Gupta, V. A. Analysis of Skeletal Muscle Defects in Larval Zebrafish by Birefringence and Touch evoke Escape Response Assays. J. Vis. Exp. 82, e50925 (2013).","journal-title":"J. Vis. Exp."},{"key":"BFsrep20466_CR19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1293\/tox.2013-0032","volume":"27","author":"XG Chen","year":"2014","unstructured":"Chen, X. G., Wang, Y. H., Wen, C. C. & Chen, Y. H. Overdose of D-serine Induces Movement Disorder and Neuromuscular Changes of Zebrafish Larvae. J. Toxicol. Pathol. 27, 19\u201324 (2014).","journal-title":"J. Toxicol. Pathol."},{"key":"BFsrep20466_CR20","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/cne.21381","volume":"503","author":"MA Fox","year":"2007","unstructured":"Fox, M. A. & Sanes, J. Synaptotagmin I and II Are Present in Distinct Subsets of Central Synapses. J. Comp. Neurol. 503, 280\u2013296 (2007).","journal-title":"J. Comp. Neurol."},{"key":"BFsrep20466_CR21","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/(SICI)1096-9861(19990412)406:3<415::AID-CNE9>3.0.CO;2-2","volume":"406","author":"D Fashena","year":"1999","unstructured":"Fashena, D. & Westerfield, M. Secondary motoneuron axons localize DM-GRASP on their fasciculated segments. J. Comp. Neurol. 406, 415\u2013 424 (1999).","journal-title":"J. Comp. Neurol."},{"key":"BFsrep20466_CR22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.nmd.2012.12.007","volume":"23","author":"B Kierdaszuk","year":"2013","unstructured":"Kierdaszuk, B. et al. A novel mutation in the DNM2 gene impairs dynamin 2 localization in skeletal muscle of a patient with late onset centronuclear myopathy. Neurumuscul. Disord. 23, 219\u2013228 (2013).","journal-title":"Neurumuscul. Disord"},{"key":"BFsrep20466_CR23","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1002\/humu.21086","volume":"30","author":"M Bitoun","year":"2009","unstructured":"Bitoun, M. et al. Dynamin 2 Mutations Associated With Human Diseases Impair Clathrin-Mediated Receptor Endocytosis. Hum. Mutat. 30, 1419\u201327 (2009).","journal-title":"Hum. Mutat."},{"key":"BFsrep20466_CR24","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.nmd.2008.01.005","volume":"18","author":"M Bitoun","year":"2008","unstructured":"Bitoun, M. et al. A novel mutation in the dynamin 2 gene in a Charcot-Marie-Tooth type 2 patient: Clinical and pathological findings. Neuromuscul. Disord. 18, 334\u2013338 (2008).","journal-title":"Neuromuscul. Disord"},{"key":"BFsrep20466_CR25","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/humu.22067","volume":"33","author":"J Bohm","year":"2012","unstructured":"Bohm, J. et al. Mutation Spectrum in the Large GTPase Dynamin 2 and Genotype\u2013Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy. Hum. Mutat. 33, 949\u2013959 (2012).","journal-title":"Hum. Mutat."},{"key":"BFsrep20466_CR26","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/ana.21235","volume":"62","author":"M Bitoun","year":"2007","unstructured":"Bitoun, M. et al. Dynamin2 mutations cause sporadic centronuclear myopathy with neonatal onset. Ann. Neurol. 62, 666\u2013670 (2007).","journal-title":"Ann. Neurol."},{"key":"BFsrep20466_CR27","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1038\/ng1657","volume":"37","author":"M Bitoun","year":"2005","unstructured":"Bitoun, M. et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat. Genet. 37, 1207\u20131209 (2005).","journal-title":"Nat. Genet."},{"key":"BFsrep20466_CR28","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1006\/dbio.1997.8604","volume":"187","author":"CE Beattie","year":"1997","unstructured":"Beattie, C. E. et al. Temporal separation in the specification of primary and secondary motoneurons in zebrafish. Dev. Biol. 187, 171\u2013182 (1997).","journal-title":"Dev. Biol."},{"key":"BFsrep20466_CR29","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1006\/dbio.2002.0852","volume":"252","author":"J Zeller","year":"2002","unstructured":"Zeller, J. et al. Migration of Zebrafish Spinal Motor Nerves into the Periphery Requires Multiple Myotome-Derived Cues. Dev. Biol. 252, 241\u2013256 (2002).","journal-title":"Dev. Biol."},{"key":"BFsrep20466_CR30","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.pneurobio.2014.03.001","volume":"118","author":"PJ Babin","year":"2014","unstructured":"Babin, P. J., Goizet, C. & Raldua, D. Zebrafish models of human motor neuron diseases: advantages and limitations. Prog. Neurobiol. 118, 36\u201358 (2014).","journal-title":"Prog. Neurobiol."},{"key":"BFsrep20466_CR31","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1523\/JNEUROSCI.12-05-01859.1992","volume":"12","author":"DW Liu","year":"1992","unstructured":"Liu, D. W. & Westerfield, M. Clustering of muscle acetylcholine receptors requires motoneurons in live embryos, but not in cell culture. J. Neurosci. 12, 1859\u20131866 (1992).","journal-title":"J. Neurosci."},{"key":"BFsrep20466_CR32","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1242\/dev.114.4.825","volume":"114","author":"SH Pike","year":"1992","unstructured":"Pike, S. H., Melancon, E. F. & Eisen, J. S. Pathfinding by zebrafish motoneurons in the absence of normal pioneer axons. Development. 114, 825\u2013831 (1992).","journal-title":"Development."},{"key":"BFsrep20466_CR33","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.ydbio.2005.06.027","volume":"285","author":"JA Panzer","year":"2005","unstructured":"Panzer, J. A. et al. Neuromuscular synaptogenesis in wild-type and mutant zebrafish. Dev. Bio. 285, 340\u2013357 (2005).","journal-title":"Dev. Bio"},{"key":"BFsrep20466_CR34","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1242\/dev.01123","volume":"131","author":"JL LeFebvre","year":"2004","unstructured":"LeFebvre, J. L. et al. Increased neuromuscular activity causes axonal defects and muscular degeneration. Development. 131, 2605\u20132618 (2004).","journal-title":"Development."},{"key":"BFsrep20466_CR35","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1093\/brain\/awl071","volume":"129","author":"D Fischer","year":"2006","unstructured":"Fischer, D. et al. Characterization of the muscle involvement in dynamin 2-related centronuclear myopathy. Brain. 129, 1463\u20131469 (2006).","journal-title":"Brain."},{"key":"BFsrep20466_CR36","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.nmd.2007.06.467","volume":"17","author":"A Echaniz-Laguna","year":"2007","unstructured":"Echaniz-Laguna, A. et al. Subtle central and peripheral nervous system abnormalities in a family with centronuclear myopathy and a novel dynamin 2 gene mutation. Neuromuscul Disord. 17, 955\u2013959 (2007).","journal-title":"Neuromuscul Disord"},{"key":"BFsrep20466_CR37","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1212\/01.wnl.0000265820.51075.61","volume":"69","author":"GM Fabrizi","year":"2007","unstructured":"Fabrizi, G. M. et al. Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease. Neurology. 69, 291\u2013295 (2007).","journal-title":"Neurology."},{"key":"BFsrep20466_CR38","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/79951","volume":"26","author":"A Nasevicius","year":"2000","unstructured":"Nasevicius, A. & Ekker, S. C. Effective targeted gene \u2018knockdown\u2019 in zebrafish. Nat. Genet. 26, 216\u2013220 (2000).","journal-title":"Nat. Genet."},{"key":"BFsrep20466_CR39","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.ntt.2007.05.001","volume":"29","author":"H Tsay","year":"2007","unstructured":"Tsay H., Wang Y., Chen, W., Huang M. & Chen Y. Treatment with sodium benzoate leads to malformation of zebrafish larvae. Neurotoxicol. Teratol. 29, 562\u2013569 (2007).","journal-title":"Neurotoxicol. Teratol."},{"key":"BFsrep20466_CR40","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods. 9, 676\u201382 (2012).","journal-title":"Nat. Methods."},{"key":"BFsrep20466_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pgen.1000372","volume":"5","author":"JJ Dowling","year":"2009","unstructured":"Dowling, J. J. et al. Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy. PLoS Genet. 5, 1\u201313 (2009).","journal-title":"PLoS Genet."},{"key":"BFsrep20466_CR42","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1242\/dev.123.1.399","volume":"123","author":"M Granato","year":"1996","unstructured":"Granato, M. et al. Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva. Development. 123, 399\u2013413 (1996).","journal-title":"Development."},{"key":"BFsrep20466_CR43","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.bbrc.2012.06.040","volume":"423","author":"J Berger","year":"2012","unstructured":"Berger, J., Sztal, T. & Currie, P. D. Quantification of birefringence readily measures the level of muscle damage in zebrafish. Biochem. Biophys. Res. Commun. 423, 785\u2013788 (2012).","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep20466","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20466.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20466.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:27:50Z","timestamp":1672838870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep20466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,4]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFsrep20466"],"URL":"https:\/\/doi.org\/10.1038\/srep20466","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,4]]},"assertion":[{"value":"14 June 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20466"}}