PUBLICATION
Zebrafish as a Model to Investigate Dynamin 2-Related Diseases
- Authors
- Bragato, C., Gaudenzi, G., Blasevich, F., Pavesi, G., Maggi, L., Giunta, M., Cotelli, F., Mora, M.
- ID
- ZDB-PUB-160205-3
- Date
- 2016
- Source
- Scientific Reports 6: 20466 (Journal)
- Registered Authors
- Cotelli, Franco
- Keywords
- Genetic testing, Neuromuscular disease
- MeSH Terms
-
- Alternative Splicing
- Animals
- Animals, Genetically Modified
- Charcot-Marie-Tooth Disease/genetics
- Charcot-Marie-Tooth Disease/pathology*
- Disease Models, Animal*
- Dynamin II/deficiency*
- Dynamin II/genetics*
- Dynamin II/metabolism
- Dynamins/genetics*
- Dynamins/metabolism
- Gene Knockdown Techniques
- Humans
- Muscle Cells/metabolism
- Muscle Cells/pathology
- Mutation
- Myopathies, Structural, Congenital/genetics
- Myopathies, Structural, Congenital/pathology*
- Sequence Homology, Nucleic Acid
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 26842864 Full text @ Sci. Rep.
Citation
Bragato, C., Gaudenzi, G., Blasevich, F., Pavesi, G., Maggi, L., Giunta, M., Cotelli, F., Mora, M. (2016) Zebrafish as a Model to Investigate Dynamin 2-Related Diseases. Scientific Reports. 6:20466.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping