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While little is known regarding the function or expression pattern of MNS1 in the embryo, co\u2010immunoprecipitation experiments in sperm have determined that MNS1 interacts with ciliary proteins, which are also important during development. Establishment of morphogenic gradients is dependent on normal ciliary motion in the primitive node beginning during gastrulation (gestational day [GD] 7 in the mouse, second\u2013third week of pregnancy in humans), a critical window for face, eye, and brain development and particularly susceptible to perturbations of developmental signals. The current study investigates the role of <jats:italic>Mns1<\/jats:italic> in craniofacial defects associated with gastrulation\u2010stage alcohol exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>On GD7, pregnant <jats:italic>Mns1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> dams were administered 2 doses of ethanol (5.8\u00a0g\/kg total) or vehicle 4\u00a0hours apart to target gastrulation. On GD17, fetuses were examined for ocular defects by scoring each eye on a scale from 1 to 7 (1\u00a0=\u00a0normal, 2 to 7\u00a0=\u00a0defects escalating in severity). Craniofacial and brain abnormalities were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prenatal alcohol exposure (PAE) significantly increased the rate of defects in wild\u2010type fetuses, as PAE fetuses had an incidence rate of 41.18% compared to a 10% incidence rate in controls. Furthermore, PAE interacted with genotype to significantly increase the defect rate and severity in <jats:italic>Mns1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> (64.29%) and <jats:italic>Mns1<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/\u2212<\/jats:sup> mice (92.31%). PAE <jats:italic>Mns1<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/\u2212<\/jats:sup> fetuses with severe eye defects also presented with craniofacial dysmorphologies characteristic of fetal alcohol syndrome and midline tissue loss in the brain, palate, and nasal septum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrate that a partial or complete knockdown of <jats:italic>Mns1<\/jats:italic> interacts with PAE to increase the susceptibility to ocular defects and correlating craniofacial and brain anomalies, likely though interaction of alcohol with motile cilia function. These results further our understanding of genetic risk factors that may underlie susceptibility to teratogenic exposures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13876","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:30:47Z","timestamp":1534951847000},"page":"2136-2143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Knockdown of <i>Mns1<\/i> Increases Susceptibility to Craniofacial Defects Following Gastrulation\u2010Stage Alcohol Exposure in Mice"],"prefix":"10.1111","volume":"42","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 University of North Carolina Chapel Hill North 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