{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:44:17Z","timestamp":1790779457264,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T00:00:00Z","timestamp":1547424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WE 2720\/4\u20101 and"],"award-info":[{"award-number":["WE 2720\/4\u20101 and"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WE 2720\/2\u20102 to HBW"],"award-info":[{"award-number":["WE 2720\/2\u20102 to HBW"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proteolipid protein (PLP) is the most abundant integral membrane protein in central nervous system (CNS) myelin. Expression of the <jats:italic>Plp<\/jats:italic>\u2010gene in oligodendrocytes is not essential for the biosynthesis of myelin membranes but required to prevent axonal pathology. This raises the question whether the exceptionally high level of PLP in myelin is required later in life, or whether high\u2010level PLP expression becomes dispensable once myelin has been assembled. Both models require a better understanding of the turnover of PLP in myelin in vivo. Thus, we generated and characterized a novel line of tamoxifen\u2010inducible <jats:italic>Plp<\/jats:italic>\u2010mutant mice that allowed us to determine the rate of PLP turnover after developmental myelination has been completed, and to assess the possible impact of gradually decreasing amounts of PLP for myelin and axonal integrity. We found that 6 months after targeting the <jats:italic>Plp<\/jats:italic>\u2010gene the abundance of PLP in CNS myelin was about halved, probably reflecting that myelin is slowly turned over in the adult brain. Importantly, this reduction by 50% was sufficient to cause the entire spectrum of neuropathological changes previously associated with the developmental lack of PLP, including myelin outfoldings, lamellae splittings, and axonal spheroids. In comparison to axonopathy and gliosis, the infiltration of cytotoxic T\u2010cells was temporally delayed, suggesting a corresponding chronology also in the genetic disorders of PLP\u2010deficiency. High\u2010level abundance of PLP in myelin throughout adult life emerges as a requirement for the preservation of white matter integrity.<\/jats:p>","DOI":"10.1002\/glia.23549","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T08:02:05Z","timestamp":1547452925000},"page":"634-649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Maintenance of high proteolipid protein level in adult central nervous system myelin is required to preserve the integrity of myelin and axons"],"prefix":"10.1002","volume":"67","author":[{"given":"Katja A.","family":"L\u00fcders","sequence":"first","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"},{"name":"G\u00f6ttingen Graduate School for Neurosciences Biophysics and Molecular Biosciences  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nessler","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Kusch","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Patzig","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona B.","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-7165","authenticated-orcid":false,"given":"Wiebke","family":"M\u00f6bius","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"},{"name":"Center for Nanoscale Microscopy and Molecular Physiology of the Brain  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8724-9666","authenticated-orcid":false,"given":"Klaus\u2010Armin","family":"Nave","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"},{"name":"Center for Nanoscale Microscopy and Molecular Physiology of the Brain  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7710-5738","authenticated-orcid":false,"given":"Hauke B.","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.01.017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220104110"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0040-x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00116.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-08-05502.1995"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1019697506757"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-0958-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22561"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.17.6287"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-011-0080-y"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900057"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20893"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200312012"},{"issue":"2","key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0021-9258(18)55985-8","article-title":"Proteolipides, a new type of tissue lipoproteins; their isolation from brain","volume":"191","author":"Folch J.","year":"1951","journal-title":"The Journal of Biological Chemistry"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(81)91097-0"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6182-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80360-8"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf043"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00820.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34783"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5369.1610"},{"issue":"21","key":"e_1_2_7_23_1","first-page":"4686","article-title":"Pathogenic inflammation in the CNS of mice carrying human plp1 mutations","volume":"25","author":"Groh J.","year":"2016","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2011.01363.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0120-6"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3390"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1921-06.2006"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042554"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3360-14.2014"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-266-7_15"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-009-8071-2"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97032"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-24-07920.1996"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90358-1"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1989.tb08558.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90148-K"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)80046-5"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1069-12.2012"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3581-06.2006"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0031-y"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001180207"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/proteomes5010003"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1706-x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00029-0"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.03.019"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23193"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23931"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.12.023"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.07.007"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254960"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-06-02265.2003"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90289-2"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(10)96020-2"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.02.027"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1740925X0900009X"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.16.5665"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-013101"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22520"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17119"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4016-11.2011"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22922"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.01.005"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90610"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90214-3"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.17.1.208"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(83)90233-6"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.09.008"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-257"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22005"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/358758a0"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4160"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.1.143"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.053"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3216-08.2009"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1939.127.2.211"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.037"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7773"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.050"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1990.tb42377.x"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01511"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1998.tb00200.x"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22456"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1254-07.2007"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399408000677"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.011"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200509174"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20010115)63:2<151::AID-JNR1007>3.0.CO;2-Y"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80138-5"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.01.006"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.23549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.23549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:31:54Z","timestamp":1694658714000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.23549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,14]]},"references-count":88,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/glia.23549"],"URL":"https:\/\/doi.org\/10.1002\/glia.23549","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,14]]},"assertion":[{"value":"2018-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}