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.

Bragato, C., Gaudenzi, G., Blasevich, F., Pavesi, G., Maggi, L., Giunta, M., et al. (2016). Zebrafish as a Model to Investigate Dynamin 2-Related Diseases. SCIENTIFIC REPORTS, 6(1), 1-13 [10.1038/srep20466].

Zebrafish as a Model to Investigate Dynamin 2-Related Diseases

Bragato, C;
2016

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.
No
Articolo in rivista - Articolo scientifico
Scientifica
Alternative Splicing; Animals; Animals, Genetically Modified; Charcot-Marie-Tooth Disease; Dynamin II; Dynamins; Gene Knockdown Techniques; Humans; Muscle Cells; Mutation; Myopathies, Structural, Congenital; Sequence Homology, Nucleic Acid; Zebrafish; Zebrafish Proteins; Disease Models, Animal; Multidisciplinary
English
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13
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Bragato, C., Gaudenzi, G., Blasevich, F., Pavesi, G., Maggi, L., Giunta, M., et al. (2016). Zebrafish as a Model to Investigate Dynamin 2-Related Diseases. SCIENTIFIC REPORTS, 6(1), 1-13 [10.1038/srep20466].
Bragato, C; Gaudenzi, G; Blasevich, F; Pavesi, G; Maggi, L; Giunta, M; Cotelli, F; Mora, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/204756
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