{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:38:56Z","timestamp":1778924336597,"version":"3.51.4"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA023508"],"award-info":[{"award-number":["R01AA023508"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fetal alcohol spectrum disorders (<jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>) have a strong genetic component although the genes that underlie this are only beginning to be elucidated. In the present study, one of the most common phenotypes of <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>, cell death within the early developing neural tube, was examined across a genetic reference population in a reverse genetics paradigm with the goal of identifying genetic loci that could influence ethanol (EtOH)\u2010induced apoptosis in the early developing neural tube.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BXD<\/jats:styled-content> recombinant inbred mice as well as the parental strains were used to evaluate genetic differences in EtOH\u2010induced cell death after exposure on embryonic day 9.5. Dams were given either 5.8\u00a0g\/kg EtOH or isocaloric maltose\u2010dextrin in 2 doses via intragastric gavage. Embryos were collected 7\u00a0hours after the initial exposure and cell death evaluated via <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> staining in the brainstem and forebrain. Genetic loci were evaluated using quantitative trait locus (<jats:styled-content style=\"fixed-case\">QTL<\/jats:styled-content>) analysis at GeneNetwork.org.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant strain differences were observed in the levels of EtOH\u2010induced cell death that were due to genetic effects and not confounding variables such as differences in developmental maturity or cell death kinetics. Comparisons between the 2 regions of the developing neural tube showed little genetic correlation with the <jats:styled-content style=\"fixed-case\">QTL<\/jats:styled-content> maps exhibiting no overlap. Significant <jats:styled-content style=\"fixed-case\">QTL<\/jats:styled-content>s were found on murine mid\u2010chromosome 4 and mid\u2010chromosome 14 only in the brainstem. Within these chromosomal loci, a number of interesting candidate genes were identified that could mediate this differential sensitivity including <jats:italic>Nfia<\/jats:italic> (nuclear factor I\/A) and <jats:italic>Otx2<\/jats:italic> (orthodenticle homeobox 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These studies demonstrate that the levels of EtOH\u2010induced cell death occur in strain\u2010 and region\u2010dependent manners. Novel <jats:styled-content style=\"fixed-case\">QTL<\/jats:styled-content>s on mouse Chr4 and Chr14 were identified that modulate the differential sensitivity to EtOH\u2010induced apoptosis in the embryonic brainstem. The genes underlying these <jats:styled-content style=\"fixed-case\">QTL<\/jats:styled-content>s could identify novel molecular pathways that are critical in this phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13947","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T16:51:48Z","timestamp":1545929508000},"page":"439-452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Influences on the Amount of Cell Death in the Neural Tube of BXD Mice Exposed to Acute Ethanol at Midgestation"],"prefix":"10.1111","volume":"43","author":[{"given":"Emilie T.","family":"Th\u00e9berge","sequence":"first","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics  British Columbia Children's Research Institution University of British Columbia Vancouver British Columbia 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