Proceedings of the National Academy of Sciences - PNAS, 2012-12, Vol.109 (49), p.20065-20070
2012
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- Autor(en) / Beteiligte
- Titel
- Mouse mtDNA mutant model of Leber hereditary optic neuropathy
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-12, Vol.109 (49), p.20065-20070
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1217113109Titel-ID: cdi_pnas_primary_109_49_20065
- Format
- –
- Schlagworte
- Adenosine triphosphatase, adenosine triphosphate, Adenosine Triphosphate - metabolism, Age Factors, animal models, Animals, atrophy, Axons, Biochemistry, Biological Sciences, Cell lines, Demyelinating Diseases - etiology, Demyelinating Diseases - pathology, Disease Models, Animal, DNA, Mitochondrial - genetics, Electroretinography, Genetic mutation, Humans, Immunoblotting, Leber hereditary optic atrophy, Mice, Mitochondria, Mitochondrial DNA, mutants, Mutation, Mutation, Missense - genetics, NADH Dehydrogenase - genetics, nerve fibers, Optic atrophy, Optic Atrophy, Hereditary, Leber - complications, Optic Atrophy, Hereditary, Leber - genetics, Optic Atrophy, Hereditary, Leber - physiopathology, Optic nerve, Optic Nerve - pathology, Oxidative stress, Oxidative Stress - physiology, pathophysiology, peripheral nervous system diseases, reactive oxygen species, Reactive Oxygen Species - metabolism, Retina, Retina - pathology, Rodents, Synaptosomes, Synaptosomes - metabolism