{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:19:42Z","timestamp":1788610782954,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,2,9]],"date-time":"2011-02-09T00:00:00Z","timestamp":1297209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Alcohol (ethanol) is a teratogen known to affect the developing eyes, face, and brain. Among the ocular defects in fetal alcohol spectrum disorder (FASD) are microphthalmia and optic nerve hypoplasia. Employing zebrafish as an FASD model provides an excellent system to analyze the molecular basis of prenatal ethanol exposure\u2010induced defects because embryos can be exposed to ethanol at defined developmental stages and affected genetic pathways can be examined. We have previously shown that disruption of <jats:italic>agrin<\/jats:italic> function in zebrafish embryos produces microphthalmia and optic nerve hypoplasia.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Zebrafish embryos were exposed to varying concentrations of ethanol in the absence or presence of morpholino oligonucleotides (MOs) that disrupt <jats:italic>agrin<\/jats:italic> function. In situ hybridization was used to analyze ocular gene expression as a consequence of ethanol exposure and <jats:italic>agrin<\/jats:italic> knockdown. Morphologic analysis of zebrafish embryos was also conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Acute ethanol exposure induces diminished <jats:italic>agrin<\/jats:italic> gene expression in zebrafish eyes and, importantly, combined treatment with subthreshold levels of <jats:italic>agrin<\/jats:italic> MO and ethanol produces pronounced microphthalmia, markedly reduces <jats:italic>agrin<\/jats:italic> gene expression, and perturbs <jats:italic>Pax6a<\/jats:italic> and <jats:italic>Mbx<\/jats:italic> gene expression. Microphthalmia produced by combined <jats:italic>agrin<\/jats:italic> MO and ethanol treatment was rescued by sonic hedgehog (<jats:italic>Shh<\/jats:italic>) mRNA overexpression, suggesting that ethanol\u2010mediated disruption of <jats:italic>agrin<\/jats:italic> expression results in disrupted <jats:italic>Shh<\/jats:italic> function.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>These studies illustrate the strong potential for using zebrafish as a model to aid in defining the molecular basis for ethanol's teratogenic effects. The results of this work suggest that <jats:italic>agrin<\/jats:italic> expression and function may be a target of ethanol exposure during embryogenesis. Birth Defects Research (Part A), 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20766","type":"journal-article","created":{"date-parts":[[2011,2,9]],"date-time":"2011-02-09T14:29:25Z","timestamp":1297261765000},"page":"129-141","source":"Crossref","is-referenced-by-count":48,"title":["<i>Agrin<\/i> function associated with ocular development is a target of ethanol exposure in embryonic zebrafish"],"prefix":"10.1002","volume":"91","author":[{"given":"Chengjin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qwan M.","family":"Turton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanta","family":"Mackinnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen 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