{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:01:40Z","timestamp":1779174100448,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T00:00:00Z","timestamp":1363132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:p>Tuberous sclerosis complex (TSC) is a genetic disease characterized by multiorgan benign tumors as well as neurological manifestations. Epilepsy and autism are two of the more prevalent neurological complications and are usually severe. TSC is caused by mutations in either the <jats:italic>TSC1<\/jats:italic> (encodes hamartin) or the <jats:italic>TSC2<\/jats:italic> (encodes tuberin) genes with <jats:italic>TSC2<\/jats:italic> mutations being associated with worse outcomes. Tuberin contains a highly conserved GTPase\u2010activating protein (GAP) domain that indirectly inhibits mammalian target of rapamycin complex 1 (mTORC1). mTORC1 dysregulation is currently thought to cause much of the pathogenesis in TSC but mTORC1\u2010independent mechanisms may also contribute. We generated a novel conditional allele of <jats:italic>Tsc2<\/jats:italic> by flanking exons 36 and 37 with loxP sites. Mice homozygous for this knock\u2010in <jats:italic>Tsc2<\/jats:italic> allele are viable and fertile with normal appearing growth and development. Exposure to Cre recombinase then creates an in\u2010frame deletion involving critical residues of the GAP domain. Homozygous conditional mutant mice generated using <jats:italic>Emx1<jats:sup>Cre<\/jats:sup><\/jats:italic> have increased cortical mTORC1 signaling, severe developmental brain anomalies, seizures, and die within 3 weeks. We found that the normal levels of the mutant <jats:italic>Tsc2<\/jats:italic> mRNA, though GAP\u2010deficient tuberin protein, appear unstable and rapidly degraded. This novel animal model will allow further study of tuberin function including the requirement of the GAP domain for protein stability. genesis 51:284\u2013292. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvg.22377","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T12:46:26Z","timestamp":1359463586000},"page":"284-292","source":"Crossref","is-referenced-by-count":23,"title":["Conditional and domain\u2010specific inactivation of the <i>Tsc2<\/i> gene in neural progenitor cells"],"prefix":"10.1002","volume":"51","author":[{"given":"Cary","family":"Fu","sequence":"first","affiliation":[{"name":"Division of Child Neurology and Epilepsy Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Vanderbilt University School of Medicine Nashville Tennessee"},{"name":"Department of Neurology Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Vanderbilt University School of Medicine Nashville Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin C.","family":"Ess","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Epilepsy Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Vanderbilt University School of Medicine Nashville Tennessee"},{"name":"Department of Neurology Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Vanderbilt University School of Medicine Nashville Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,13]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.52.37400"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-012-1785-x"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204009"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.08.024"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.07.018"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738040190091301"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra055323"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<106::AID-GENE30>3.0.CO;2-T"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhr300"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411768200"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn325"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20271"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.25.2899"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1110003"},{"key":"e_1_2_4_18_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291702007092"},{"key":"e_1_2_4_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.12.2155"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6451"},{"key":"e_1_2_4_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.749203"},{"key":"e_1_2_4_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.09.008"},{"key":"e_1_2_4_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1991"},{"key":"e_1_2_4_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0955-08.2008"},{"key":"e_1_2_4_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.03.036"},{"key":"e_1_2_4_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2682"},{"key":"e_1_2_4_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7319"},{"key":"e_1_2_4_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5351.707"},{"key":"e_1_2_4_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2008.01.001"},{"key":"e_1_2_4_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.351605"},{"key":"e_1_2_4_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00329-4"},{"key":"e_1_2_4_32_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-0192"},{"key":"e_1_2_4_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10283"},{"key":"e_1_2_4_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds156"},{"key":"e_1_2_4_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq491"}],"container-title":["genesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvg.22377","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvg.22377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T10:42:49Z","timestamp":1700649769000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dvg.22377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,13]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1002\/dvg.22377"],"URL":"https:\/\/doi.org\/10.1002\/dvg.22377","archive":["Portico"],"relation":{},"ISSN":["1526-954X","1526-968X"],"issn-type":[{"value":"1526-954X","type":"print"},{"value":"1526-968X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,13]]}}}