{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:33:13Z","timestamp":1780378393501,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Ly\u20101 antibody reactive clone (LYAR) is a nucleolar zinc finger protein that has been implicated in cell growth, self\u2010renewal of embryonic stem cells, and medulloblastoma. To test whether LYAR is critical for cell growth and development, we generated <jats:italic>Lyar<\/jats:italic> mutant mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Mice carrying the mutant <jats:italic>Lyar<\/jats:italic><jats:sup><jats:italic>gt<\/jats:italic><\/jats:sup> allele were generated from embryonic stem cells that contained a gene\u2010trap insertion in the <jats:italic>Lyar<\/jats:italic> gene. Phenotypic analyses were performed on <jats:italic>Lyar<\/jats:italic> mutant mice and mouse embryonic fibroblasts. <jats:italic>Lyar<\/jats:italic><jats:sup><jats:italic>gt\/gt<\/jats:italic><\/jats:sup> mice were crossed to mice lacking the p53 tumor suppressor protein and <jats:italic>Lyar\/p53<\/jats:italic> compound mutants scored for external abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:italic>Lyar<\/jats:italic><jats:sup><jats:italic>gt\/gt<\/jats:italic><\/jats:sup> homozygotes are viable, fertile, and indistinguishable from wild type littermates. However, the growth of <jats:italic>Lyar<\/jats:italic><jats:sup>+\/<jats:italic>gt<\/jats:italic><\/jats:sup> and <jats:italic>Lyar<\/jats:italic><jats:sup><jats:italic>gt\/gt<\/jats:italic><\/jats:sup> mouse embryonic fibroblasts (MEFs) was impaired, coincident with an increase in the steady\u2010state level of p53 and a key p53 effector of growth arrest, p21, suggesting that a cellular stress response is triggered in the absence of a wild type level of LYAR. Remarkably, the majority of <jats:italic>Lyar<\/jats:italic><jats:sup>+\/<jats:italic>gt<\/jats:italic><\/jats:sup> and <jats:italic>Lyar<\/jats:italic><jats:sup><jats:italic>gt\/gt<\/jats:italic><\/jats:sup> female mice lacking <jats:italic>p53<\/jats:italic> mice failed to survive. The neural tube defect (NTD) exencephaly was observed in \u224826% and \u224861% of female <jats:italic>Lyar<\/jats:italic><jats:sup>+\/<jats:italic>gt;<\/jats:italic><\/jats:sup><jats:italic>p53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Lyar<\/jats:italic><jats:sup><jats:italic>gt\/gt;<\/jats:italic><\/jats:sup><jats:italic>p53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> embryos, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p><jats:italic>Lyar\/p53<\/jats:italic> mutant mice represent a new digenic model of NTDs. Furthermore, these studies identify <jats:italic>Lyar<\/jats:italic> as a novel candidate gene for a role in human NTDs. These results provide new data to support the idea that loss of a p53\u2010mediated developmental checkpoint may increase the risk of NTDs owing to some germline mutations. \u00a9 Birth Defects Research (Part A) 94:729\u2013737, 2012. Published 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23048","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T20:34:35Z","timestamp":1342816475000},"page":"729-737","source":"Crossref","is-referenced-by-count":16,"title":["Mutations in <i>Lyar<\/i> and <i>p53<\/i> are synergistically lethal in female mice"],"prefix":"10.1002","volume":"94","author":[{"given":"Guan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Fulkerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Malek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ghassemifar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul 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