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Our study profiled gene expression in gastrulation-stage embryos from two commonly used, genetically similar mouse substrains, C57BL\/6J (6J) and C57BL\/6NHsd (6N), that differ in alcohol sensitivity. First, we established normal gene expression patterns at three finely resolved time points during gastrulation and developed a web-based interactive tool. Baseline transcriptional differences across strains were associated with immune signaling. Second, we examined the gene networks impacted by alcohol in each strain. Alcohol caused a more pronounced transcriptional effect in the 6J versus 6N mice, matching the increased susceptibility of the 6J mice. The 6J strain exhibited dysregulation of pathways related to cell death, proliferation, morphogenic signaling and craniofacial defects, while the 6N strain showed enrichment of hypoxia and cellular metabolism pathways. These datasets provide insight into the changing transcriptional landscape across mouse gastrulation, establish a valuable resource that enables the discovery of candidate genes that may modify alcohol susceptibility that can be validated in humans, and identify novel pathogenic mechanisms of alcohol.<\/jats:p><jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.049012","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T13:54:52Z","timestamp":1622123692000},"source":"Crossref","is-referenced-by-count":31,"title":["Transcriptomic analyses of gastrulation-stage mouse embryos with differential susceptibility to alcohol"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5838-0016","authenticated-orcid":false,"given":"Karen E.","family":"Boschen","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-0149","authenticated-orcid":false,"given":"Travis S.","family":"Ptacek","sequence":"additional","affiliation":[{"name":"Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-3273","authenticated-orcid":false,"given":"Matthew E.","family":"Berginski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-1663","authenticated-orcid":false,"given":"Jeremy M.","family":"Simon","sequence":"additional","affiliation":[{"name":"Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2038-6548","authenticated-orcid":false,"given":"Scott E.","family":"Parnell","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"2021061813133074600_DMM049012C1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0892-0362(88)90060-8","article-title":"Fetal alcohol syndrome in families","volume":"10","author":"Abel","year":"1988","journal-title":"Neurotoxicol. 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