Expression of mitofusin 2R94Q in a transgenic mouse leads to Charcot–Marie–Tooth neuropathy type 2A (original) (raw)
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11 Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland
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22 Department of Medical Genetics, University of Lausanne, 27 Rue du Bugnon, 1005 Lausanne, Switzerland
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22 Department of Medical Genetics, University of Lausanne, 27 Rue du Bugnon, 1005 Lausanne, Switzerland
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22 Department of Medical Genetics, University of Lausanne, 27 Rue du Bugnon, 1005 Lausanne, Switzerland
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33 Division of Clinical Epidemiology, Geneva University Hospitals, University of Geneva, rue Gabrielle Perret-Gentil 4, 1211 Genève 14, Switzerland
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22 Department of Medical Genetics, University of Lausanne, 27 Rue du Bugnon, 1005 Lausanne, Switzerland
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11 Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland
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Received:
09 November 2009
Revision received:
15 February 2010
Cite
Romain Cartoni, Estelle Arnaud, Jean-Jacques Médard, Olivier Poirot, Delphine S. Courvoisier, Roman Chrast, Jean-Claude Martinou, Expression of mitofusin 2R94Q in a transgenic mouse leads to Charcot–Marie–Tooth neuropathy type 2A, Brain, Volume 133, Issue 5, May 2010, Pages 1460–1469, https://doi.org/10.1093/brain/awq082
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Abstract
Charcot–Marie–Tooth disease type 2A is an autosomal dominant axonal form of peripheral neuropathy caused by mutations in the mitofusin 2 gene. Mitofusin 2 encodes a mitochondrial outer membrane protein that participates in mitochondrial fusion in mammalian cells. How mutations in this protein lead to Charcot–Marie–Tooth disease type 2A pathophysiology remains unclear. We have generated a transgenic mouse expressing either a mutated (R94Q) or wild-type form of human mitofusin 2 in neurons to evaluate whether the R94Q mutation was sufficient for inducing a Charcot–Marie–Tooth disease type 2A phenotype. Only mice expressing mitofusin 2R94Q developed locomotor impairments and gait defects thus mimicking the Charcot–Marie–Tooth disease type 2A neuropathy. In these animals, the number of mitochondria per axon was significantly increased in the distal part of the sciatic nerve axons with a diameter smaller than 3.5 μm. Importantly, the analysis of R94Q transgenic animals also revealed an age-related shift in the size of myelinated axons leading to an over-representation of axons smaller than 3.5 μm. Together these data suggest a link between an increased number of mitochondria in axons and a shift in axonal size distribution in mitofusin 2R94Q transgenic animals that may contribute to their neurological phenotype.
© The Author (2010). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected]
Topic:
- phenotype
- charcot-marie-tooth disease
- mutation
- animals, transgenic
- mitochondria
- axon
- motor and sensory neuropathy type i, hereditary
- mice, transgenic
- myelin sheath
- neurons
- sciatic nerve
- mice
- neuropathy
- mfn2 gene
- diameter
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