{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:10:57Z","timestamp":1791223857092,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"2","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"}],"funder":[{"name":"IBMS\/PUMC Director's Fund","award":["2007RC03"],"award-info":[{"award-number":["2007RC03"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["30970602"],"award-info":[{"award-number":["30970602"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Novel Drug Development Fund","award":["2009ZX09303-008"],"award-info":[{"award-number":["2009ZX09303-008"]}]},{"DOI":"10.13039\/501100013314","name":"111 Project","doi-asserted-by":"crossref","award":["B08007."],"award-info":[{"award-number":["B08007."]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>\n                    Nijmegen breakage syndrome (NBS), caused by mutation of the\n                    <jats:italic>Nbn<\/jats:italic>\n                    gene, is a recessive genetic disorder characterized by immunodeficiency, elevated sensitivity to ionizing radiation, chromosomal instability, microcephaly, and high predisposition to malignancies. To explore the underlying molecular mechanisms of NBS microcephaly, Frappart et al. previously inactivated\n                    <jats:italic>Nbn<\/jats:italic>\n                    gene in the central nervous system (CNS) of mice by the nestin\u2010Cre targeting gene system and generated\n                    <jats:italic>Nbn<\/jats:italic>\n                    <jats:sup>CNS\u2010del<\/jats:sup>\n                    mice. Here we first report that\n                    <jats:italic>Nbn<\/jats:italic>\n                    gene inactivation induces the defective proliferation and enhanced apoptosis of the oligodendrocyte precursor cells (OPCs), contributing to the severe hypomyelination of the nerve fibers of the corpus callosum. Under conditions of DNA damage and oxidative stress, the distinct regulatory roles of ATM\u2010Chk2 signaling and AKT\/mTOR signaling are responsible for the defective proliferation and enhanced apoptosis of the Nbn\u2010deficient OPCs. In addition, specific HDAC isoforms may play distinctive roles in regulating the myelination of the Nbn\u2010deficient OPCs. However, brain\u2010derived neurotrophic factor and nerve growth factor stimulation attenuates the oxidative stress and thereby increases the proliferation of the Nbn\u2010deficient OPCs, which is accompanied by upregulation of the AKT\/mTOR\/P70S6K signaling pathway. Taken together, these findings demonstrate that DNA damage and oxidative stress resulting from\n                    <jats:italic>Nbn<\/jats:italic>\n                    gene inactivation are associated with hypomyelination of the nerve fibers of corpus callosum. \u00a9 2013 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jnr.23313","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T04:04:43Z","timestamp":1385352283000},"page":"254-266","source":"Crossref","is-referenced-by-count":17,"title":["DNA damage and oxidative injury are associated with hypomyelination in the corpus callosum of newborn Nbn\n                    <sup>CNS\u2010del<\/sup>\n                    mice"],"prefix":"10.1002","volume":"92","author":[{"given":"B.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.Q.","family":"Wang","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Age Research\u2010Fritz Lipmann Institute Jena Germany"},{"name":"Faculty of Biology\u2010Pharmacy Friedrich\u2010Schiller\u2010University Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.M.","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 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