{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:30:16Z","timestamp":1781101816489,"version":"3.54.1"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,12,19]]},"abstract":"<jats:p>\n                    We report a method for introducing mtDNA mutations into the\n mouse female germ line by means of embryonic stem (ES) cell cybrids.\n Mitochondria were recovered from the brain of a NZB mouse by fusion of\n synaptosomes to a mtDNA-deficient (\u03c1\u00b0) cell line. These cybrids\n were enucleated and the cytoplasts were electrofused to rhodamine-6G\n (R-6G)-treated female ES cells. The resulting ES cell cybrids permitted\n transmission of the NZB mtDNAs through the mouse maternal lineage for\n three generations. Similarly, mtDNAs from a partially\n respiratory-deficient chloramphenicol-resistant (CAP\n                    <jats:sup>R<\/jats:sup>\n                    ) cell\n line also were introduced into female chimeric mice and were\n transmitted to the progeny. CAP\n                    <jats:sup>R<\/jats:sup>\n                    chimeric mice developed a\n variety of ocular abnormalities, including congenital cataracts,\n decreased retinal function, and hamaratomas of the optic nerve. The\n germ-line transmission of the CAP\n                    <jats:sup>R<\/jats:sup>\n                    mutation resulted in\n animals with growth retardation, myopathy, dilated cardiomyopathy, and\n perinatal or\n                    <jats:italic>in utero<\/jats:italic>\n                    lethality. Skeletal and heart\n muscle mitochondria of the CAP\n                    <jats:sup>R<\/jats:sup>\n                    mice were enlarged and\n atypical with inclusions. This mouse ES cell-cybrid approach now\n provides the means to generate a wide variety of mouse models of\n mitochondrial disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.250491597","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"14461-14466","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":106,"title":["Maternal germ-line transmission of mutant mtDNAs from embryonic stem cell-derived chimeric mice"],"prefix":"10.1073","volume":"97","author":[{"given":"James E.","family":"Sligh","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn E.","family":"Levy","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina G.","family":"Waymire","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulette","family":"Allard","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirck L.","family":"Dillehay","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Nusinowitz","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Heckenlively","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant R.","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Departments of\r Dermatology and Pathology and Division of\r Animal Resources, Emory University School of Medicine, 1462 Clifton\r Road, Atlanta, GA 30322; and Jules Stein Eye Institute,\r Harbor-UCLA Medical Center, Torrance, CA 90509"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,12,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-376"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-226"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-159"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.3.846"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(00)00161-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0398-231"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1482"},{"key":"e_1_3_3_8_2","first-page":"277","volume-title":"Emery and Rimoin's Principles and Practice of Medical Genetics","author":"Wallace D C","year":"1996","unstructured":"D C Wallace, M D Brown, M T Lott Emery and Rimoin's Principles and Practice of Medical Genetics, eds D L Rimoin, J M Connor, R E Pyeritz, A E H Emery (Churchill Livingstone, London) 1, 277\u2013332 (1996)."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/9.21.5785"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.10.5113"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008967412955"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/11403"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.16.4848"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018431316831"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-146"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-93"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/82826"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90385-R"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.10.2164"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.5.1681"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90198-7"},{"key":"e_1_3_3_22_2","first-page":"113","volume-title":"Teratocarcinomas and Embryonic Stem Cells. 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