{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:44:47Z","timestamp":1779345887308,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,1,3]],"date-time":"2004-01-03T00:00:00Z","timestamp":1073088000000},"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":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Individuals with tuberous sclerosis complex (TSC) exhibit a variety of neurologic abnormalities, including mental retardation, epilepsy, and autism. Examination of human TSC brains demonstrate dysplastic astrocytes and neurons, areas of abnormal neuronal migration (tubers), and hamartomatous growths, termed subependymal nodules, which can progress to subependymal giant cell astrocytomas (SEGA). Previous studies have suggested that these neuropathologic features may result from abnormal neuroglial cell differentiation. In an effort to provide support for this hypothesis and to identify specific markers of aberrant neuroglial cell differentiation in TSC, we employed gene expression profiling on <jats:italic>Tsc1<\/jats:italic> conditional knockout (<jats:italic>Tsc1<\/jats:italic><jats:sup>GFAP<\/jats:sup>CKO) mouse astrocytes. We identified several transcripts implicated in central nervous system development that are differentially expressed in <jats:italic>Tsc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes compared to wild\u2010type astrocytes. We validated the differential expression of select transcripts on the protein level both in primary cultures of <jats:italic>Tsc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes and in <jats:italic>Tsc1<\/jats:italic><jats:sup>GFAP<\/jats:sup>CKO mouse brains. Moreover, we show that these markers are also differentially expressed within cortical tubers, but not in adjacent normal tissue from TSC patient brains. This study provides supportive evidence for a developmental defect in neuroglial cell differentiation relevant to the genesis of TSC nervous system pathology and underscores the utility of mouse modeling for understanding the molecular pathogenesis of human disease. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10324","type":"journal-article","created":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T08:01:48Z","timestamp":1078128108000},"page":"28-40","source":"Crossref","is-referenced-by-count":37,"title":["Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology"],"prefix":"10.1002","volume":"46","author":[{"given":"Kevin C.","family":"Ess","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik J.","family":"Uhlmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Declue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter B.","family":"Crino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,1,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1136(200103)33:3<205::AID-GLIA1019>3.0.CO;2-D"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.14.5100-5113.2002"},{"key":"e_1_2_6_5_1","first-page":"907","article-title":"MR imaging of tuberous sclerosis in neonates and young infants","volume":"20","author":"Baron Y","year":"1999","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.7.1384"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.14152"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(01)00300-X"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00007-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0248-4900(02)00006-0"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202035899"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)03078-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81172-1"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb847"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00007431"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10145"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9962"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315012"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/302381"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151033798"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00365-0"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1242\/dev.120.9.2637","article-title":"The expression pattern of a novel gene encoding brain\u2010fatty acid binding protein correlates with neuronal and glial cell development","volume":"120","author":"Kurtz A","year":"1994","journal-title":"Development"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.525"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvf170"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10579"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205024"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050438"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.6.2213-2224.2003"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002470050693"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(01)00304-7"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00138-0"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00132-8"},{"key":"e_1_2_6_33_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s004010000269","article-title":"Developmental expression of the tuberous sclerosis proteins tuberin and hamartin","volume":"101","author":"Murthy V","year":"2001","journal-title":"Acta Neuropathol (Berl)"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.25.2889"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/35055553"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7319"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050691"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4685-6_25"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-11-04223.1997"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00520-7"},{"key":"e_1_2_6_41_1","first-page":"277","article-title":"Cdk5 on the brain","volume":"12","author":"Smith DS","year":"2001","journal-title":"Cell Growth Differ"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200004000-00001"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-02-00550.2001"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202476899"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5972"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10283"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.805"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0916"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.10324","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.10324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T19:39:39Z","timestamp":1696793979000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.10324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1,3]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1002\/glia.10324"],"URL":"https:\/\/doi.org\/10.1002\/glia.10324","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1,3]]}}}