Expression of mitofusin 2(R94Q) in a transgenic mouse leads to Charcot-Marie-Tooth neuropathy type 2A
| Autor: | Delphine S. Courvoisier, Olivier Poirot, Jean-Claude Martinou, Estelle Arnaud, Roman Chrast, Jean-Jacques Médard, Romain Cartoni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Aging
Glutamine Neurons/metabolism Mitochondrion medicine.disease_cause Mitochondrial Membrane Transport Proteins Nerve Fibers Myelinated GTP Phosphohydrolases Mice 0302 clinical medicine Charcot-Marie-Tooth Disease Membrane Transport Proteins/genetics Axon Neurons 0303 health sciences Mutation Axons/ultrastructure Sciatic Nerve Mitochondria Cell biology Charcot-Marie-Tooth Disease/genetics/pathology/physiopathology Mitochondria/ultrastructure Phenotype medicine.anatomical_structure mitochondrial fusion Mitochondrial Proteins/genetics Sciatic nerve Genetically modified mouse DNA Complementary Transgene DNA Complementary/metabolism Mice Transgenic Biology Arginine Mitochondrial Proteins 03 medical and health sciences ddc:570 medicine Animals Humans Peripheral Nerves 030304 developmental biology Nerve Fibers Myelinated/pathology Sciatic Nerve/pathology Membrane Transport Proteins GTP Phosphohydrolases/genetics medicine.disease Axons Peripheral Nerves/ultrastructure Microscopy Electron Peripheral neuropathy Charcot-Marie-Tooth Disease/genetics Charcot-Marie-Tooth Disease/pathology nervous system Neurology (clinical) Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Brain, vol. 133, no. Pt 5, pp. 1460-1469 Brain : a journal of neurology Brain Brain, Vol. 133, No Pt 5 (2010) pp. 1460-1469 |
| ISSN: | 0006-8950 |
| Popis: | 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 2(R94Q) 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 microm. 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 microm. Together these data suggest a link between an increased number of mitochondria in axons and a shift in axonal size distribution in mitofusin 2(R94Q) transgenic animals that may contribute to their neurological phenotype. |
| Databáze: | OpenAIRE |
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