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These malformations, such as a deficient philtrum, are exemplified by a loss of midline tissue and correspond, at least in part, to regionally selective cell death in the embryo. The tumor suppressor protein Tp53 is an important mechanism for cell death, but the role of Tp53 in the consequences of alcohol exposure during the gastrulation stage has yet to be examined. The current studies used mice and zebrafish to test whether genetic loss of <jats:italic>Tp53<\/jats:italic> is a conserved mechanism to protect against the effects of early developmental stage alcohol exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female mice, heterozygous for a mutation in the <jats:italic>Tp53<\/jats:italic> gene, were mated with <jats:italic>Tp53<\/jats:italic> heterozygous males, and the resulting embryos were exposed during gastrulation on gestational day 7 (GD 7) to alcohol (two maternal injections of 2.9\u00a0g\/kg, i.p., 4\u00a0h apart) or a vehicle control. Zebrafish mutants or heterozygotes for the <jats:italic>tp53<jats:sup>zdf1<\/jats:sup><\/jats:italic>\u00a0M214K mutation and their wild\u2010type controls were exposed to alcohol (1.5% or 2%) beginning 6\u00a0h postfertilization (hpf), the onset of gastrulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Examination of GD 17\u00a0mice revealed that eye defects were the most common phenotype among alcohol\u2010exposed fetuses, occurring in nearly 75% of the alcohol\u2010exposed wild\u2010type fetuses. <jats:italic>Tp53<\/jats:italic> gene deletion reduced the incidence of eye defects in both the heterozygous and mutant fetuses (to about 35% and 20% of fetuses, respectively) and completely protected against alcohol\u2010induced facial malformations. Zebrafish (4 days postfertilization) also demonstrated alcohol\u2010induced reductions of eye size and trabeculae length that were less common and less severe in <jats:italic>tp53<\/jats:italic> mutants, indicating a protective effect of <jats:italic>tp53<\/jats:italic> deletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results identify an evolutionarily conserved role of Tp53 as a pathogenic mechanism for alcohol\u2010induced teratogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14688","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T09:56:57Z","timestamp":1632823017000},"page":"1965-1979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Loss of tumor protein 53 protects against alcohol\u2010induced facial malformations in mice and zebrafish"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6598-5654","authenticated-orcid":false,"given":"Eric W.","family":"Fish","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4590-484X","authenticated-orcid":false,"given":"Scott K.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences Waggoner Center for Alcohol and Addiction Research and Institute for Neuroscience University of Texas Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-9021","authenticated-orcid":false,"given":"Rachel L.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5258-2477","authenticated-orcid":false,"given":"Johann K.","family":"Eberhart","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences Waggoner Center for Alcohol and Addiction Research and Institute for Neuroscience University of Texas Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Parnell","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina USA"},{"name":"Department of Cell Biology and Physiology University of North Carolina Chapel Hill North Carolina USA"},{"name":"Carolina Institute for Developmental Disabilities University of North Carolina Chapel Hill North Carolina 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