title: Zebrafish as a Model to Investigate Dynamin 2-Related Diseases.
abstract: Mutations in the dynamin-2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM) and dominant intermediate Charcot-Marie-Tooth (CMT) neuropathy type B (CMTDIB). As the relation between these DNM2-related diseases is poorly understood, we used zebrafish to investigate the effects of two different DNM2 mutations. First we identified a new alternatively spliced zebrafish dynamin-2a mRNA (dnm2a-v2) with greater similarity to human DNM2 than the deposited sequence. Then we knocked-down the zebrafish dnm2a, producing defects in muscle morphology. Finally, we expressed two mutated DNM2 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 DNM2 in vivo.
authors: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Neurological Institute C. Besta, Milano, Italy.
authors: Cinzia
authors: C
authors: Bragato
authors: Department of Biosciences, University of Milan, Via Celoria, 26, 20133, Milan, Italy.
authors: Germano
authors: G
authors: Gaudenzi
authors: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Neurological Institute C. Besta, Milano, Italy.
authors: Flavia
authors: F
authors: Blasevich
authors: Department of Biosciences, University of Milan, Via Celoria, 26, 20133, Milan, Italy.
authors: Giulio
authors: G
authors: Pavesi
authors: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Neurological Institute C. Besta, Milano, Italy.
authors: Lorenzo
authors: L
authors: Maggi
authors: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Neurological Institute C. Besta, Milano, Italy.
authors: Michele
authors: M
authors: Giunta
authors: Department of Biosciences, University of Milan, Via Celoria, 26, 20133, Milan, Italy.
authors: Franco
authors: F
authors: Cotelli
authors: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Neurological Institute C. Besta, Milano, Italy.
authors: Marina
authors: M
authors: Mora
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D030801:Animals, Genetically Modified; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D034285:Dynamin II / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D034281:Dynamins / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics / Q000473:pathology*; D012689:Sequence Homology, Nucleic Acid; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins