{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:57:25Z","timestamp":1760061445437,"version":"3.37.3"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,9]],"date-time":"2015-02-09T00:00:00Z","timestamp":1423440000000},"content-version":"vor","delay-in-days":8,"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"}]}],"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>Prenatal alcohol exposure can kill developing neurons, leading to microencephaly and mental retardation. However, not all fetuses are equally vulnerable to alcohol's neurotoxic effects. While some fetuses are severely affected and are ultimately diagnosed with fetal alcohol syndrome (FAS), others have no evidence of neuropathology and are behaviorally normal. These widely different outcomes among alcohol\u2010exposed fetuses are likely due, in part, to genetic differences. Some fetuses possess genotypes that make them much more vulnerable than others to alcohol's teratogenic effects. However, to date, only 1 gene has been identified whose mutation can worsen alcohol\u2010induced behavioral deficits in an animal model of FAS. That gene is neuronal nitric oxide synthase (<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content>). The purpose of this study was to determine whether mutation of <jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content> can likewise worsen alcohol\u2010induced microencephaly and lead to permanent neuronal deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type and nNOS<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; the results of which are reported in the companion paper. The brains were then weighed, and stereological cell counts were performed on the cerebral cortex and hippocampal formation, which are the brain regions that mediate the aforementioned behavioral tasks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol caused dose\u2010dependent microencephaly, but only in the nNOS<jats:sup>\u2212\/\u2212<\/jats:sup> mice and not in wild\u2010type mice. Alcohol\u2010induced neuronal losses were more severe in the nNOS<jats:sup>\u2212\/\u2212<\/jats:sup> mice than in the wild\u2010type mice in all of the brain regions examined, including the cerebral cortex, hippocampal CA3 subregion, hippocampal CA1 subregion, and dentate gyrus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Targeted mutation of the <jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content> gene increases the vulnerability of the developing brain to alcohol\u2010induced growth restriction and neuronal losses. This increased neuropathology is associated with worsened behavioral dysfunction. The results demonstrate the critical importance of genotype in determining the outcome of developmental alcohol exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12615","type":"journal-article","created":{"date-parts":[[2015,2,9]],"date-time":"2015-02-09T11:57:28Z","timestamp":1423483048000},"page":"221-231","source":"Crossref","is-referenced-by-count":19,"title":["Genetic Absence of nNOS Worsens Fetal Alcohol Effects in Mice. 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