{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:28:12Z","timestamp":1778585292359,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,14]],"date-time":"2015-02-14T00:00:00Z","timestamp":1423872000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AA021465"],"award-info":[{"award-number":["RO1 AA021465"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John Martin Fund for Neuroanatomic Research","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alcohol abuse during pregnancy often induces neuropsychological problems in the offspring, including learning disorders, attention deficits, and behavior problems, all of which are prominent components of fetal alcohol spectrum disorders (FASD). However, not all children who were exposed to alcohol in utero are equally affected by it. While some children have major deficits, others are spared. This unequal vulnerability is likely due largely to differences in fetal genetics. Some fetuses appear to have certain genotypes that make them much more prone to FASD. However, to date, no gene has been identified that worsens alcohol\u2010induced brain dysfunction. Nitric oxide (NO) is a gaseous molecule that can protect developing neurons against alcohol\u2010induced death. In the brain, NO is produced by neuronal nitric oxide synthase (<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content>). In this study, we examined whether homozygous mutation of the<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content>gene in mice worsens the behavioral deficits of developmental alcohol exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type and<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup>mice received alcohol (0.0, 2.2, or 4.4\u00a0mg\/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests, including open field activity, the Morris water maze, and paired pulse inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For the wild\u2010type mice, alcohol impaired performance only in the water maze. In contrast, for the<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup>mice, alcohol impaired performance on all 3 tasks. Furthermore, the<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup>mice were substantially more impaired than wild\u2010type mice in their performance on all 3 of the behavioral tests and at both the low (2.2) and high (4.4) doses of alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Targeted disruption of the<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content>gene worsens the behavioral impact of developmental alcohol exposure and allows alcohol\u2010induced learning problems to emerge that are not seen in wild type. This is the first demonstration that a specific genotype can interact with alcohol to worsen functional brain deficits in an animal model of FASD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12616","type":"journal-article","created":{"date-parts":[[2015,2,14]],"date-time":"2015-02-14T06:18:57Z","timestamp":1423894737000},"page":"212-220","source":"Crossref","is-referenced-by-count":6,"title":["Genetic Absence of<scp>nNOS<\/scp>Worsens Fetal Alcohol Effects in Mice. 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