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 journalArticle

98 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20065-20070
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number49
DOIs
Publication statusPublished - Dec 4 2012

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Leber's Hereditary Optic Atrophy
Mitochondrial DNA
Reactive Oxygen Species
Optic Atrophy
Mutation
Synaptosomes
Demyelinating Diseases
Optic Nerve
Nerve Fibers
Mitochondria
Respiration
Oxidative Stress
Animal Models
Adenosine Triphosphate

Keywords

  • Maternal inheritance
  • Neurodegenerative disease
  • Ophthalmology
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • General

Cite this

Mouse mtDNA mutant model of Leber hereditary optic neuropathy. / Lin, Chun Shi; Sharpley, Mark S.; Fan, Weiwei; Waymire, Katrina G.; Sadun, Alfredo A.; Carelli, Valerio; Ross-Cisneros, Fred N.; Baciu, Peter; Sung, Eric; McManus, Meagan J.; Pan, Billy X.; Gil, Daniel W.; MacGregor, Grant R.; Wallace, Douglas C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 49, 04.12.2012, p. 20065-20070.

Research output: Contribution to journalArticle

Lin, CS, Sharpley, MS, Fan, W, Waymire, KG, Sadun, AA, Carelli, V, Ross-Cisneros, FN, Baciu, P, Sung, E, McManus, MJ, Pan, BX, Gil, DW, MacGregor, GR & Wallace, DC 2012, 'Mouse mtDNA mutant model of Leber hereditary optic neuropathy', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 49, pp. 20065-20070. https://doi.org/10.1073/pnas.1217113109
Lin, Chun Shi ; Sharpley, Mark S. ; Fan, Weiwei ; Waymire, Katrina G. ; Sadun, Alfredo A. ; Carelli, Valerio ; Ross-Cisneros, Fred N. ; Baciu, Peter ; Sung, Eric ; McManus, Meagan J. ; Pan, Billy X. ; Gil, Daniel W. ; MacGregor, Grant R. ; Wallace, Douglas C. / Mouse mtDNA mutant model of Leber hereditary optic neuropathy. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 49. pp. 20065-20070.
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