TY - JOUR
T1 - Mice hemizygous for a pathogenic mitofusin- 2 allele exhibit hind limb/foot gait deficits and phenotypic perturbations in nerve and muscle
AU - Bannerman, Peter
AU - Burns, Travis
AU - Xu, Jie
AU - Miers, Laird
AU - Pleasure, David E
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0167573
DO - 10.1371/journal.pone.0167573
M3 - Article
C2 - 27907123
AN - SCOPUS:85000417054
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 12
M1 - e0167573
ER -