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PLoS One. 2016 Dec 1;11(12):e0167573. doi: 10.1371/journal.pone.0167573. eCollection 2016.

Mice Hemizygous for a Pathogenic Mitofusin-2 Allele Exhibit Hind Limb/Foot Gait Deficits and Phenotypic Perturbations in Nerve and Muscle.

Author information

1
Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, Sacramento, California, United States of America.
2
Department of Cell Biology and Human Anatomy, University of California Davis, Davis, California, United States of America.
3
Department of Neurology, University of California Davis, Sacramento, California, United States of America.

Abstract

Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele. Crossing these mice with nestin-Cre transgenic mice elicited T105M MFN2 expression in neuroectoderm, and resulted in diminished numbers of mitochondria in peripheral nerve axons, an alteration in skeletal muscle fiber type distribution, and a gait abnormality.

PMID:
27907123
PMCID:
PMC5132404
DOI:
10.1371/journal.pone.0167573
[Indexed for MEDLINE]
Free PMC Article

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