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In gastrulation, which occurs during the third week of human pregnancy, alcohol targets the ectoderm, the precursor of the eyes, face, and brain. This midline tissue loss leads to the craniofacial dysmorphologies, such as microphthalmia and a smooth philtrum, which define fetal alcohol syndrome (FAS). An important regulator of alcohol\u2010induced cell death is the pro\u2010apoptotic protein Bax. The current study determines if mice lacking the <jats:italic>Bax<\/jats:italic> gene are less susceptible to the pathogenic effects of gastrulation\u2010stage alcohol exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male and female <jats:italic>Bax<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice mated to produce embryos with full (<jats:sup>\u2212\/\u2212<\/jats:sup>) or partial (<jats:sup>+\/\u2212<\/jats:sup>) <jats:italic>Bax<\/jats:italic> deletions, or <jats:italic>Bax<\/jats:italic><jats:sup>+\/+<\/jats:sup> wild\u2010type controls. On Gestational Day 7 (GD 7), embryos received two alcohol (2.9\u00a0g\/kg, 4 hr apart), or control exposures. A subset of embryos was collected 12\u2009hr later and examined for the presence of apoptotic cell death, while others were examined on GD 17 for the presence of FAS\u2010like facial features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Full <jats:italic>Bax<\/jats:italic> deletion reduced embryonic apoptotic cell death and the incidence of fetal eye and face malformations, indicating that Bax normally facilitates the development of alcohol\u2010induced defects. An RNA\u2010seq analysis of GD 7 <jats:italic>Bax<\/jats:italic><jats:sup>+\/+<\/jats:sup> and <jats:italic>Bax<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> embryos revealed 63 differentially expressed genes, some of which may interact with the <jats:italic>Bax<\/jats:italic> deletion to further protect against apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, these experiments identify that Bax is a primary teratogenic mechanism of gastrulation\u2010stage alcohol exposure.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2009","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T11:50:23Z","timestamp":1649505023000},"page":"1229-1243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The pro\u2010apoptotic <i>Bax<\/i> gene modifies susceptibility to craniofacial dysmorphology following gastrulation\u2010stage alcohol 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