title: Mice Hemizygous for a Pathogenic Mitofusin-2 Allele Exhibit Hind Limb/Foot Gait Deficits and Phenotypic Perturbations in Nerve and Muscle.
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.
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, Sacramento, California, United States of America.|Department of Cell Biology and Human Anatomy, University of California Davis, Davis, California, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Bannerman
authors.affiliation: Department of Neurology, University of California Davis, Sacramento, California, United States of America.
authors.forename: Travis
authors.initials: T
authors.lastname: Burns
authors.affiliation: Department of Neurology, University of California Davis, Sacramento, California, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, University of California Davis, Sacramento, California, United States of America.
authors.forename: Laird
authors.initials: L
authors.lastname: Miers
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, Sacramento, California, United States of America.|Department of Neurology, University of California Davis, Sacramento, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D001370:Axonal Transport; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000235:genetics*; D005684:Gait; D005786:Gene Expression Regulation; D057898:Hemizygote; D006614:Hindlimb / Q000473:pathology; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism
chemical_list: C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C577485:Nes protein, mouse; D064231:Nestin; D022661:RNA, Untranslated; C045073:Cre recombinase; D019426:Integrases; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse