{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:21:22Z","timestamp":1790846482523,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,23]],"date-time":"2013-11-23T00:00:00Z","timestamp":1385164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:p>Nijmegen Breakage Syndrome (NBS) is a recessive genetic disorder characterized by immunodeficiency, elevated sensitivity to ionizing radiation, chromosomal instability, microcephaly, and high predisposition to malignancies. Since the underlying molecular mechanisms of the NBS microcephaly are still obscure, thus our group previously inactivated the <jats:italic>Nbn<\/jats:italic> gene in the central nervous system (CNS) of mice by nestin\u2010Cre targeting gene system, and generated <jats:italic>Nbn<\/jats:italic><jats:sup>CNS\u2010del<\/jats:sup> mice. Interestingly, the newborn <jats:italic>Nbn<\/jats:italic><jats:sup>CNS\u2010del<\/jats:sup> mice exhibit obvious microcephaly, which is accompanied by severe ataxia and balance deficiency. In this study presented here, we report that Nbn\u2010deficiency induces the enhanced apoptosis of the mature oligodendrocytes at postnatal day 7, which further affects the myelination of the nerve fibers of cerebrum and corpus callosum.The distinct regulatory roles of Ataxia telangiectasia mutated (ATM) signaling and protein kinase B(Akt)\/the mammalian target of Rapamycin (AKT\/mTOR) signaling are responsible for the enhanced apoptosis of the Nbn\u2010deficient oligodendrocytes. In addition, a series of transcriptional factors including histonedeacetylase (HDAC), zinc finger protein 191 (ZFP\u2010191) and myelin sheath regulatory factor (MRF) play distinct roles in regulating the myelination of the Nbn\u2010deficient oligodendrocytes. Based on these results, it concludes that ATM\u2010Chk2\u2010P53\u2010P21 signaling pathway and the AKT\/mTOR signaling pathway are both responsible for the enhanced apoptosis of the Nbn\u2010deficient oligodendrocytes. HDAC, ZFP\u2010191, and MRF are also involved in the pathogenesis of the hypomyelination of the Nbn\u2010deficient oligodendrocytes. GLIA 2014;62:133\u2013144<\/jats:p>","DOI":"10.1002\/glia.22593","type":"journal-article","created":{"date-parts":[[2013,11,23]],"date-time":"2013-11-23T06:09:20Z","timestamp":1385186960000},"page":"133-144","source":"Crossref","is-referenced-by-count":8,"title":["<i>Nbn<\/i> gene inactivation in the CNS of mouse inhibits the myelinating ability of the mature cortical oligodendrocytes"],"prefix":"10.1002","volume":"62","author":[{"given":"Bo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology, Center for Experimental Animal Research Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology Emory University  Atlanta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Age Research\u2010Fritz Lipmann Institute Friedrich\u2010Schiller\u2010University Jena  Germany"},{"name":"Faculty of Biology\u2010Pharmacy Friedrich\u2010Schiller\u2010University Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Min","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Center for Experimental Animal Research Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1998.0685"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.09.021"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.07.006"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00211-7"},{"key":"e_1_2_6_6_1","first-page":"S1568","article-title":"The role of DNA repair in brain related disease pathology","author":"Canugovi C","year":"2013","journal-title":"DNA Repair"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81175-7"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1242\/dev.126.18.4027","article-title":"Loss of p27Kip1 function results in increased proliferative capacity of oligodendrocyte progenitors but unaltered timing of differentiation","volume":"126","author":"Casaccia-Bonnefil P","year":"1999","journal-title":"Development"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-08-02933.1998"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm805"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.204172"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.19.4758"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.004"},{"key":"e_1_2_6_14_1","first-page":"2013","article-title":"Purification and culture of oligodendrocyte lineage cells","volume":"1","author":"Dugas JC","year":"2013","journal-title":"Cold Spring Harb Protoc"},{"key":"e_1_2_6_15_1","first-page":"7263","article-title":"Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation\u2010induced tumorigenesis","volume":"63","author":"Dumon-Jones V","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03442"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0150-08.2008"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.09.005"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1228"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20520"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-011-9494-6"},{"key":"e_1_2_6_22_1","first-page":"471","article-title":"TOR signaling in growth and metabolism","volume":"124","author":"Harris TE","year":"2003","journal-title":"Cell"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1864510"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.5604\/17322693.1029530"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00808-5"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1069-12.2012"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05767.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1359"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2011.01.030"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108297"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.3"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-013-9971-2"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20729"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2559"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0232-09.2009"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702162200"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20530"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2006.04.003"},{"key":"e_1_2_6_39_1","first-page":"895","article-title":"Mammalian target of rapamycin: master regulator of cell growth in the nervous system","volume":"22","author":"Sandsmark DK","year":"2007","journal-title":"Histol Histopathol"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320200410"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600504"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3047"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2007.08.015"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.37"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.2.153"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81174-5"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1981.tb05740.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/146493"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601411"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610185200"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2333"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2011.10.021"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.22593","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.22593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:51:45Z","timestamp":1696603905000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.22593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,23]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1002\/glia.22593"],"URL":"https:\/\/doi.org\/10.1002\/glia.22593","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,23]]}}}