Mice hemizygous for a pathogenic mitofusin- 2 allele exhibit hind limb/foot gait deficits and phenotypic perturbations in nerve and muscle

Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David E Pleasure

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Article numbere0167573
JournalPLoS One
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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