Mouse mtDNA mutant model of Leber hereditary optic neuropathy
CS Lin, MS Sharpley, W Fan… - Proceedings of the …, 2012 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2012•National Acad Sciences
An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing
the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation
exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in
central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal
accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial
analysis revealed partial complex I and respiration defects and increased reactive oxygen …
the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation
exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in
central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal
accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial
analysis revealed partial complex I and respiration defects and increased reactive oxygen …
An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.
National Acad Sciences