{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:10:38Z","timestamp":1791443438395,"version":"4.3.3"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"49","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,12,4]]},"abstract":"<jats:p>\n                    An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA\n                    <jats:italic>ND6<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1217113109","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T00:57:15Z","timestamp":1352163435000},"page":"20065-20070","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":228,"title":["Mouse mtDNA mutant model of Leber hereditary optic neuropathy"],"prefix":"10.1073","volume":"109","author":[{"given":"Chun Shi","family":"Lin","sequence":"first","affiliation":[{"name":"Center for Mitochondrial and Epigenomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104;"},{"name":"Center for Molecular and Mitochondrial Medicine and Genetics and Department of Biological Chemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Sharpley","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial and Epigenomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104;"},{"name":"Center for Molecular and Mitochondrial Medicine and Genetics and Department of Biological Chemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Fan","sequence":"additional","affiliation":[{"name":"Center for Molecular and Mitochondrial Medicine and Genetics and Department of Biological Chemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina G.","family":"Waymire","sequence":"additional","affiliation":[{"name":"Center for Molecular and Mitochondrial Medicine and Genetics and Department of Biological Chemistry, University of California, Irvine, CA 92697;"},{"name":"Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo A.","family":"Sadun","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neurological Surgery, Doheny Eye Institute, University of Southern California (USC) Keck School of Medicine, Los Angeles, CA 90089-0228;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Carelli","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neurological Surgery, Doheny Eye Institute, University of Southern California (USC) Keck School of Medicine, Los Angeles, CA 90089-0228;"},{"name":"Istituto delle Scienze Neurologiche di Bologna, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), Bologna, Italy;"},{"name":"Department of Neurological Sciences, University of Bologna School of Medicine, Bologna, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred N.","family":"Ross-Cisneros","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neurological Surgery, Doheny Eye Institute, University of Southern California (USC) Keck School of Medicine, Los Angeles, CA 90089-0228;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Baciu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Allergan, Inc., Irvine, CA 92612; 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