{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T21:52:39Z","timestamp":1718747559156},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,9]],"date-time":"2006-02-09T00:00:00Z","timestamp":1139443200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Numerous genetically engineered mouse models for neural tube defects (NTDs) exist, and some of the implicated proteins are functionally related. For example, the growth arrest and DNA damage\u2010inducible protein Gadd45a and tumor suppressor p53 are functionally similar, and both are involved in neural tube development (<jats:italic>Gadd45a<\/jats:italic>\u2010 and <jats:italic>Trp53<\/jats:italic>\u2010null embryos show low levels of exencephaly). To assess their roles in neural tube development, we generated double\u2010null mice from <jats:italic>Gadd45a<\/jats:italic>\u2010 and <jats:italic>Trp53<\/jats:italic>\u2010null mice, as well as from <jats:italic>cyclin\u2010dependent kinase inhibitor<\/jats:italic> (<jats:italic>Cdkn1a<\/jats:italic>) (p21)\u2010null and <jats:italic>xeroderma pigmentosum group C<\/jats:italic> (<jats:italic>XPC<\/jats:italic>)\u2010null mice that do not show spontaneous exencephaly.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p><jats:italic>Gadd45a<\/jats:italic>\u2010, <jats:italic>Trp53<\/jats:italic>\u2010, <jats:italic>Cdkn1a<\/jats:italic>\u2010, and <jats:italic>XPC<\/jats:italic>\u2010null mice were crossed to generate several double\u2010null mouse models. Embryos (embryonic day [ED] 16\u201318) from the single\u2010 and double\u2010null crosses were scored for NTDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Deletion of both <jats:italic>Gadd45a<\/jats:italic> and <jats:italic>Trp53<\/jats:italic> in mice increased exencephaly frequencies compared to the deletion of either single gene (34.0% in <jats:italic>Gadd45a\/Trp53<\/jats:italic>\u2010null compared to 8.4% and 9.1% in the <jats:italic>Gadd45a<\/jats:italic>\u2010 and <jats:italic>Trp53<\/jats:italic>\u2010null embryos, respectively). Furthermore, although deletion of another p53\u2010regulated gene, <jats:italic>Cdkn1a<\/jats:italic>, is not associated with exencephaly, in conjunction with <jats:italic>Gadd45a<\/jats:italic> deletion, the exencephaly frequencies are increased (30.5% in the <jats:italic>Gadd45a\/Cdkn1a<\/jats:italic>\u2010null embryos) and are similar to those in the <jats:italic>Gadd45a<\/jats:italic>\/<jats:italic>Trp53<\/jats:italic>\u2010null embryos. Although <jats:italic>XPC<\/jats:italic> deletion increased exencephaly frequencies in <jats:italic>Trp53<\/jats:italic>\u2010null embryos, <jats:italic>XPC<\/jats:italic> deletion did not increase the exencephaly frequencies in <jats:italic>Gadd45a<\/jats:italic>\u2010null embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The increased genetic liability to exencephaly in the <jats:italic>Gadd45a\/Trp53<\/jats:italic>\u2010 and <jats:italic>Gadd45a\/Cdkn1a<\/jats:italic>\u2010null embryos may be related to the disruption of multiple cellular pathways associated with Gadd45a and p53. Birth Defects Research (Part A), 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20217","type":"journal-article","created":{"date-parts":[[2006,2,10]],"date-time":"2006-02-10T00:47:00Z","timestamp":1139532420000},"page":"129-132","source":"Crossref","is-referenced-by-count":9,"title":["Neural tube development requires the cooperation of p53\u2010 and Gadd45a\u2010associated pathways"],"prefix":"10.1002","volume":"76","author":[{"given":"Andrew D.","family":"Patterson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Hildesheim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Albert J.","family":"Fornace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Christine","family":"Hollander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,2,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.11.3859-3871.2003"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)70794-X"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.1770090403"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1181"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90039-X"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/356215a0"},{"key":"e_1_2_5_8_1","first-page":"329","article-title":"Genetic instability in animal tumorigenesis models","volume":"29","author":"Donehower LA","year":"1997","journal-title":"Cancer Surv"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5372.2107"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(99)00068-3"},{"key":"e_1_2_5_11_1","first-page":"639","article-title":"The role of the cyclin\u2010dependent kinase inhibitor p21 in apoptosis","volume":"1","author":"Gartel AL","year":"2002","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.35.102401.090432"},{"key":"e_1_2_5_13_1","first-page":"7305","article-title":"Gadd45a protects against UV irradiation\u2010induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53","volume":"62","author":"Hildesheim J","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/13802"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205774"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.4.5.1675"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.993"},{"key":"e_1_2_5_18_1","first-page":"1675","article-title":"Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1","volume":"11","author":"Kearsey JM","year":"1995","journal-title":"Oncogene"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-175"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420280115"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1148\/93.3.625"},{"key":"e_1_2_5_22_1","first-page":"1899","article-title":"Overexpression of p21WAF1\/CIP1 induces growth arrest, giant cell formation and apoptosis in human breast carcinoma cell lines","volume":"11","author":"Sheikh MS","year":"1995","journal-title":"Oncogene"},{"key":"e_1_2_5_23_1","first-page":"2255","article-title":"Antisense GADD45 expression results in decreased DNA repair and sensitizes cells to UV\u2010irradiation or cisplatin","volume":"13","author":"Smith ML","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.10.3705-3714.2000"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh541"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(99)00039-X"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.20217","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.20217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T15:36:30Z","timestamp":1697470590000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.20217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,2]]}},"alternative-id":["10.1002\/bdra.20217"],"URL":"https:\/\/doi.org\/10.1002\/bdra.20217","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,2]]}}}