{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:01:13Z","timestamp":1793275273238,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T00:00:00Z","timestamp":1435881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Thierry Latran Foundation"},{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Van Meer Stichting, Netherlands ALS Foundation"},{"name":"European Community Health Seventh Framework Program","award":["259867"],"award-info":[{"award-number":["259867"]}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"crossref","award":["Blake\/Mar12\/6088"],"award-info":[{"award-number":["Blake\/Mar12\/6088"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      How hexanucleotide (GGGGCC) repeat expansions in\n                      <jats:italic>C9ORF72<\/jats:italic>\n                      cause amyotrophic lateral sclerosis (ALS) remains poorly understood. Both gain\u2010 and loss\u2010of\u2010function mechanisms have been proposed. Evidence supporting these mechanisms in vivo is, however, incomplete. Here we determined the effect of C9orf72 loss\u2010of\u2010function in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated and analyzed a conditional\n                      <jats:italic>C9orf72<\/jats:italic>\n                      knockout mouse model.\n                      <jats:italic>\n                        C9orf72\n                        <jats:sup>fl\/fl<\/jats:sup>\n                      <\/jats:italic>\n                      mice were crossed with\n                      <jats:italic>Nestin\u2010Cre<\/jats:italic>\n                      mice to selectively remove C9orf72 from neurons and glial cells. Immunohistochemistry was performed to study motor neurons and neuromuscular integrity, as well as several pathological hallmarks of ALS, such as gliosis and TDP\u201043 mislocalization. In addition, motor function and survival were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Neural\u2010specific ablation of C9orf72 in conditional\n                      <jats:italic>C9orf72<\/jats:italic>\n                      knockout mice resulted in significantly reduced body weight but did not induce motor neuron degeneration, defects in motor function, or altered survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our data suggest that\n                      <jats:italic>C9orf72<\/jats:italic>\n                      loss\u2010of\u2010function, by itself, is insufficient to cause motor neuron disease. These results may have important implications for the development of therapeutic strategies for C9orf72\u2010associated ALS. Ann Neurol 2015;78:426\u2013438\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24453","type":"journal-article","created":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T04:34:42Z","timestamp":1433478882000},"page":"426-438","source":"Crossref","is-referenced-by-count":264,"title":["<scp>C<\/scp>\n                    9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits"],"prefix":"10.1002","volume":"78","author":[{"given":"Max","family":"Koppers","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Neurology and Neurosurgery Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Blokhuis","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Neurology and Neurosurgery Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk\u2010Jan","family":"Westeneng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margo L.","family":"Terpstra","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A. C.","family":"Zundel","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Vieira de S\u00e1","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond D.","family":"Schellevis","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Waite","sequence":"additional","affiliation":[{"name":"Institute of Psychological Medicine and Clinical Neurosciences Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University Cardiff United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Blake","sequence":"additional","affiliation":[{"name":"Institute of Psychological Medicine and Clinical Neurosciences Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University Cardiff United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H.","family":"Veldink","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard H.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Jeroen","family":"Pasterkamp","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.011"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70043-1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.02.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232927"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa9344"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000130"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts725"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu068"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23946"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.10.015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.016"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083450"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318835110"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.036"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt222"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2521-09.2009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3566"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/12703"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0481"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.113.156570"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.078790"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256800"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13124"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-014-0166-y"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24453","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24453","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.24453","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:53:50Z","timestamp":1696578830000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,3]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1002\/ana.24453"],"URL":"https:\/\/doi.org\/10.1002\/ana.24453","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,3]]}}}