{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:59:25Z","timestamp":1790521165937,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,1,7]]},"abstract":"<jats:p>\n                    A subset of patients suffering from familial amyotrophic lateral sclerosis (FALS) exhibit point mutations in the gene encoding Cu-Zn superoxide dismutase [superoxide:superoxide oxidoreductase, EC\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"ec\" xlink:href=\"1.15.1.1\">1.15.1.1<\/jats:ext-link>\n                    (SOD)]. The human wild-type and five FALS\n                    <jats:italic>Sod<\/jats:italic>\n                    mutant transgenes were introduced into the fruit fly,\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    , in a Cu-Zn\n                    <jats:italic>Sod<\/jats:italic>\n                    null background.\n                    <jats:italic>Sod<\/jats:italic>\n                    null flies had dramatically decreased life span, glutathione and methionine content, fertility, locomotor activity, and resistance to hyperoxic stress, compared with wild-type controls. All of these phenotypic manifestations were rescued fully by a single human wild-type allele, expressing 5\u201310% of wild-type SOD activity. Full recovery of wild-type life span was also observed when human mutant and wild-type alleles were placed together in the fly\n                    <jats:italic>Sod<\/jats:italic>\n                    null background. The FALS\n                    <jats:italic>Sod<\/jats:italic>\n                    mutations alone caused a recessive phenotype, usually involving low or undetectable levels of SOD activity, in which: (\n                    <jats:italic>i<\/jats:italic>\n                    ) full restoration of the wild-type phenotype was observed among young adults, and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) older adults exhibited a sudden increase in oxidative stress, accompanied by physiological impairment of abrupt onset, and followed by premature death. Thus, the minimal SOD activity associated with the FALS\n                    <jats:italic>Sod<\/jats:italic>\n                    mutations appears to determine longevity, not by chronically increasing oxidative stress, but by limiting the time in which a viable redox environment can be maintained. However, the dominant gain of function by mutant SOD, which occurs in human patients and in the transgenic mouse model of FALS, is not observed in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0136976100","type":"journal-article","created":{"date-parts":[[2003,1,7]],"date-time":"2003-01-07T12:22:42Z","timestamp":1041942162000},"page":"301-306","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Phenotypic effects of familial amyotrophic lateral sclerosis mutant\n                    <i>Sod<\/i>\n                    alleles in transgenic\n                    <i>Drosophila<\/i>"],"prefix":"10.1073","volume":"100","author":[{"given":"Robin J.","family":"Mockett","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033; and Department of Biological Sciences, Dedman Life Sciences Building, Southern Methodist University, Dallas, TX 75275"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana N.","family":"Radyuk","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033; and Department of Biological Sciences, Dedman Life Sciences Building, Southern Methodist University, Dallas, TX 75275"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith J.","family":"Benes","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033; and Department of Biological Sciences, Dedman Life Sciences Building, Southern Methodist University, Dallas, TX 75275"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Orr","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033; and Department of Biological Sciences, Dedman Life Sciences Building, Southern Methodist University, Dallas, TX 75275"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajindar S.","family":"Sohal","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033; and Department of Biological Sciences, Dedman Life Sciences Building, Southern Methodist University, Dallas, TX 75275"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90346-1"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105313442207"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8351519"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.17.8292"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5709"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69051936.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5384.1851"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01784-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.19.8574"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1993.1111"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/534"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00333-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(99)00090-1"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-10-03369.2001"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/35006074"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90177-1"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)49336-6"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(71)90370-8"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.13.1733"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(89)90192-9"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01435994"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.8.2761"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90348-2"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.11.841"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9585"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.26.15036"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(82)90518-5"},{"key":"e_1_3_3_29_2","first-page":"632","volume":"11","author":"Reveillaud I","year":"1991","unstructured":"I Reveillaud, A Niedzwiecki, K G Bensch, J E Fleming Mol Cell Biol 11, 632\u2013640 (1991).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(92)90006-Y"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0136976100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:39:45Z","timestamp":1649756385000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0136976100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,12,26]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1,7]]}},"alternative-id":["10.1073\/pnas.0136976100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0136976100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,12,26]]},"assertion":[{"value":"2002-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}