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Neuromuscul Disord. 2011 Jan;21(1):58-67. doi: 10.1016/j.nmd.2010.09.002. Epub 2010 Oct 14.

Developmental defects and neuromuscular alterations due to mitofusin 2 gene (MFN2) silencing in zebrafish: a new model for Charcot-Marie-Tooth type 2A neuropathy.

Author information

1
Department of Biology, University of Padua, Padua, Italy.

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.

PMID:
20951042
DOI:
10.1016/j.nmd.2010.09.002
[Indexed for MEDLINE]

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