ZFIN ID: ZDB-PUB-101027-4
Developmental defects and neuromuscular alterations due to mitofusin 2 gene (MFN2) silencing in zebrafish: A new model for Charcot-Marie-Tooth type 2A neuropathy
Vettori, A., Bergamin, G., Moro, E., Vazza, G., Polo, G., Tiso, N., Argenton, F., and Mostacciuolo, M.L.
Date: 2011
Source: Neuromuscular disorders : NMD   21(1): 58-67 (Journal)
Registered Authors: Argenton, Francesco, Moro, Enrico, Tiso, Natascia
Keywords: Peripheral neuropathy, CMT2A, MFN2, Zebrafish, Axonal degeneration
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/drug effects
  • Body Patterning/genetics
  • Charcot-Marie-Tooth Disease*/chemically induced
  • Charcot-Marie-Tooth Disease*/complications
  • Charcot-Marie-Tooth Disease*/genetics
  • Computational Biology
  • Developmental Disabilities/etiology*
  • Developmental Disabilities/genetics
  • Disease Models, Animal
  • Down-Regulation/drug effects*
  • Down-Regulation/genetics
  • Embryo, Nonmammalian
  • GTP Phosphohydrolases
  • Humans
  • Membrane Proteins/genetics
  • Mitochondrial Proteins/genetics
  • Motor Activity/drug effects
  • Motor Activity/genetics
  • Neuromuscular Diseases/etiology*
  • Neuromuscular Diseases/genetics
  • Oligodeoxyribonucleotides, Antisense/adverse effects*
  • RNA, Messenger/metabolism
  • Receptors, Cholinergic/metabolism
  • Tolloid-Like Metalloproteinases/genetics*
  • Tolloid-Like Metalloproteinases/metabolism
  • Tubulin/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 20951042 Full text @ Neuromuscul. Disord.
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ABSTRACT
The development of new animal models is a crucial step in determining the pathological mechanism underlying neurodegenerative diseases and is essential for the development of effective therapies. We have investigated the zebrafish (Danio rerio) as a new model to study CMT2A, a peripheral neuropathy characterized by the selective loss of motor neurons, caused by mutations of mitofusin 2 gene. Using a knock-down approach, we provide evidence that during embryonic development, mitofusin 2 loss of function is responsible of several morphological defects and motility impairment. Immunohistochemical investigations, revealing the presence of severe alterations in both motor neurons and muscles fibres, indicated the central role played by MFN2 in axonal and neuromuscular development. Finally, we demonstrated the ability of human MFN2 to balance the downregulation of endogenous mfn2 in zebrafish, further supporting the conserved function of the MFN2 gene. These results highlight the essential role of mitofusin 2 in the motor axon development and demonstrate the potential of zebrafish as a suitable and complementary platform for dissecting pathogenetic mechanisms of MFN2 mutations in vivo.
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