{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:40:23Z","timestamp":1791330023234,"version":"4.3.1"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,5,27]]},"abstract":"<jats:p>Dominant mutations in ubiquitously expressed superoxide dismutase (SOD1) cause familial ALS by provoking premature death of adult motor neurons. To test whether mutant damage to cell types beyond motor neurons is required for the onset of motor neuron disease, we generated chimeric mice in which all motor neurons and oligodendrocytes expressed mutant SOD1 at a level sufficient to cause fatal, early-onset motor neuron disease when expressed ubiquitously, but did so in a cellular environment containing variable numbers of non-mutant, non-motor neurons. Despite high-level mutant expression within 100% of motor neurons and oligodendrocytes, in most of these chimeras, the presence of WT non-motor neurons substantially delayed onset of motor neuron degeneration, increasing disease-free life by 50%. Disease onset is therefore non-cell autonomous, and mutant SOD1 damage within cell types other than motor neurons and oligodendrocytes is a central contributor to initiation of motor neuron degeneration.<\/jats:p>","DOI":"10.1073\/pnas.0802556105","type":"journal-article","created":{"date-parts":[[2008,5,20]],"date-time":"2008-05-20T23:33:39Z","timestamp":1211326419000},"page":"7594-7599","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":269,"title":["Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice"],"prefix":"10.1073","volume":"105","author":[{"given":"Koji","family":"Yamanaka","sequence":"first","affiliation":[{"name":"*Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093;"},{"name":"Yamanaka Research Unit, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Boillee","sequence":"additional","affiliation":[{"name":"*Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Garcia","sequence":"additional","affiliation":[{"name":"*Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093;"},{"name":"University of Missouri, Columbia, MO 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"McAlonis-Downes","sequence":"additional","affiliation":[{"name":"*Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver R.","family":"Mikse","sequence":"additional","affiliation":[{"name":"*Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don W.","family":"Cleveland","sequence":"additional","affiliation":[{"name":"*Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S. B.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,5,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.27.070203.144244"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.018"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1971"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-10-03369.2001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-12-04825.2002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5258-07.2008"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086071"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607423103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123511"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2047"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032539299"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705046104"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1876"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1885"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10224"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-02-00660.2000"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90259-7"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00677-3"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00678-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00926-0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80272-X"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503862102"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20888"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990920)412:2<373::AID-CNE13>3.0.CO;2-N"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609411103"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2073"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/4553"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086137"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.954"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0802556105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:47:34Z","timestamp":1649782054000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0802556105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,27]]},"references-count":29,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2008,5,27]]}},"alternative-id":["10.1073\/pnas.0802556105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0802556105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1108826.564960","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,27]]},"assertion":[{"value":"2008-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}