{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:35:19Z","timestamp":1781105719116,"version":"3.54.1"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,3,20]]},"abstract":"<jats:p>\n                    Cockayne syndrome (CS) is a rare autosomal recessive neurodegenerative disease that is associated with mutations in either of two transcription-coupled DNA repair genes,\n                    <jats:italic>CSA<\/jats:italic>\n                    or\n                    <jats:italic>CSB<\/jats:italic>\n                    . Mice with a targeted mutation in the\n                    <jats:italic>Csb<\/jats:italic>\n                    gene (Cs-b\n                    <jats:sup>m\/m<\/jats:sup>\n                    ) exhibit a milder phenotype compared with human patients with mutations in the orthologous\n                    <jats:italic>CSB<\/jats:italic>\n                    gene. Mice mutated in\n                    <jats:italic>Csb<\/jats:italic>\n                    were crossed with mice lacking\n                    <jats:italic>Xpc<\/jats:italic>\n                    (Xp-c\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ), the global genome repair gene, to enhance the pathological symptoms. These Cs-b\n                    <jats:sup>m\/m<\/jats:sup>\n                    .Xp-c\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were normal at birth but exhibited progressive failure to thrive, whole-body wasting, and ataxia and died at approximately postnatal day 21. Characterization of Cs-b\n                    <jats:sup>m\/m<\/jats:sup>\n                    .Xp-c\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    brains at postnatal stages demonstrated widespread reduction of myelin basic protein (MBP) and myelin in the sensorimotor cortex, the stratum radiatum, the corpus callosum, and the anterior commissure. Quantification of individual axons by electron microscopy showed a reduction in both the number of myelinated axons and the average diameter of myelin surrounding the axons. There were no significant differences in proliferation or oligodendrocyte differentiation between Cs-b\n                    <jats:sup>m\/m<\/jats:sup>\n                    .Xp-c\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and Cs-b\n                    <jats:sup>m\/+<\/jats:sup>\n                    .Xp-c\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Rather, Cs-b\n                    <jats:sup>m\/m<\/jats:sup>\n                    .Xp-c\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    oligodendrocytes were unable to generate sufficient MBP or to maintain the proper myelination during early development. Csb is a multifunctional protein regulating both repair and the transcriptional response to reactive oxygen through its interaction with histone acetylase p300 and the hypoxia-inducible factor (HIF)1 pathway. On the basis of our results, combined with that of others, we suggest that in Csb the transcriptional response predominates during early development, whereas a neurodegenerative response associated with repair deficits predominates in later life.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1202621109","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T23:33:43Z","timestamp":1330990423000},"page":"4627-4632","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Dysmyelination not demyelination causes neurological symptoms in preweaned mice in a murine model of Cockayne syndrome"],"prefix":"10.1073","volume":"109","author":[{"given":"Ingrid","family":"Revet","sequence":"first","affiliation":[{"name":"Departments of aDermatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luzviminda","family":"Feeney","sequence":"additional","affiliation":[{"name":"Departments of aDermatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy A.","family":"Tang","sequence":"additional","affiliation":[{"name":"Pathology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Huang","sequence":"additional","affiliation":[{"name":"Pathology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cleaver","sequence":"additional","affiliation":[{"name":"Departments of aDermatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,3,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420115"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2009.07.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2663"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.01.017"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610619104"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2004.04.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.09.009"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077232"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1179595"},{"key":"e_1_3_3_10_2","first-page":"4237","article-title":"Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome","volume":"39","author":"Lehmann AR","year":"1979","unstructured":"AR Lehmann, S Kirk-Bell, L Mayne, Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome. 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