Mouse mtDNA mutant model of Leber hereditary optic neuropathy

Chun Shi Lin, Mark S. Sharpley, Weiwei Fan, Katrina G. Waymire, Alfredo A. Sadun, Valerio Carelli, Fred N. Ross-Cisneros, Peter Baciu, Eric Sung, Meagan J. McManus, Billy X. Pan, Daniel W. Gil, Grant R. MacGregor, Douglas C. Wallace

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)20065-20070
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
Publication statusPublished - Dec 4 2012


  • Maternal inheritance
  • Neurodegenerative disease
  • Ophthalmology
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • General


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