title: Mouse mtDNA mutant model of Leber hereditary optic neuropathy.
abstract: 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.
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Chun Shi
authors.initials: CS
authors.lastname: Lin
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sharpley
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Katrina G
authors.initials: KG
authors.lastname: Waymire
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.forename: Peter
authors.initials: P
authors.lastname: Baciu
authors.forename: Eric
authors.initials: E
authors.lastname: Sung
authors.forename: Meagan J
authors.initials: MJ
authors.lastname: McManus
authors.forename: Billy X
authors.initials: BX
authors.lastname: Pan
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Gil
authors.forename: Grant R
authors.initials: GR
authors.lastname: Macgregor
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004596:Electroretinography; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D009900:Optic Nerve / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000473:pathology*; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase