{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:28:36Z","timestamp":1785461316537,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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"}]},{"name":"MSRF program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Emerging evidence has suggested that choline is an effective treatment for at least some of the neurobehavioral deficits associated with Fetal Alcohol Spectrum Disorders (FASD). However, the mechanism of how choline works to ameliorate ethanol\u2019s teratogenic effects, and whether it acts directly on the fetus or indirectly by altering the uterine environment, remains unknown. Previous work from our lab demonstrated that 4 BXD mouse strains that show high levels of ethanol-induced cell death on embryonic day 9.5 (E9.5) have differential responses to choline supplementation. This differential response in mouse strains highlights a need to further understand the role of genetics in choline metabolism. Because the liver is the central organ for choline metabolism, and the embryonic liver of mice is not functional this early in gestation, we focused on choline metabolism in the liver of the dam. Methods: Using a bioinformatics approach, the goals were to assess whether (1) genetic differences in liver choline metabolism in the dam could affect ethanol-induced cell death in a genotype-specific manner and (2) any of these candidate genes in the liver of the dam could be linked to differential response to choline amongst the strains. By performing a literature review, haplotype analysis among the 4 BXD strains, and liver protein expression analysis among 3 strains, we show that there are genetic differences in choline metabolic genes that are consistent with the hypothesis that maternal choline metabolism could mediate differential sensitivity. Results: While we identified two genes as promising candidates for the variable responses to choline supplementation among the four previously identified BXD strains choline\/ethanolamine phosphotransferase 1 (cept1) and choline transporter gene solute carrier family 44 member 1 (slc44a1), the wealth of data on slc44a1 makes it the stronger candidate and suggests that it should be further explored. Conclusions: Genetic differences in maternal choline metabolism are present and may underlie variable therapeutic responses to choline, warranting a hypothesis that requires further investigation across animal models and human populations.<\/jats:p>","DOI":"10.3390\/genes17010042","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Choline Metabolic Genes in the Liver of the Dam as Candidates for Mediating Choline\u2019s Efficacy in Mitigating Ethanol-Induced Cell Death in the Neural Tube: A Preliminary Analysis"],"prefix":"10.3390","volume":"17","author":[{"given":"Tasfia","family":"Chowdhury","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-8910","authenticated-orcid":false,"given":"David","family":"Ashbrook","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer D.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Center for Behavioral Teratology, San Diego State University, San Diego, CA 92182, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Goldowitz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Hamre","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s10597-017-0104-0","article-title":"Fetal Alcohol Spectrum Disorders: Characteristics, Complications, and Treatment","volume":"53","author":"Wilhoit","year":"2017","journal-title":"Community Ment. 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