{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:08:18Z","timestamp":1792627698023,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T00:00:00Z","timestamp":1494806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54\u2010AA019756"],"award-info":[{"award-number":["U54\u2010AA019756"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99\/R00\u2010AA018697"],"award-info":[{"award-number":["K99\/R00\u2010AA018697"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01\u2010AA021651"],"award-info":[{"award-number":["U01\u2010AA021651"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2017,7,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Genetic factors influence the physical and neurobehavioral manifestations of prenatal alcohol exposure (PAE). Animal models allow the investigation of specific genes that confer vulnerability to, or protection from, birth defects associated with fetal alcohol spectrum disorders (FASDs). The objective of the present experiments was to determine if genetic alterations in the Sonic Hedgehog (Shh) signaling pathways affect the vulnerability to PAE\u2010induced skeletal defects involving the forelimbs and\/or hindlimbs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Wild\u2010type C57BL\/6J female mice were bred with males in which one copy of the\n                      <jats:italic>Shh<\/jats:italic>\n                      or\n                      <jats:italic>Gli2<\/jats:italic>\n                      genes had been knocked out, to produce litters with both wild\u2010type (\n                      <jats:italic>+\/+<\/jats:italic>\n                      ) and heterozygous (\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                      ) embryos. Alcohol doses (two injections of 2.9 g\/kg, 4 hours apart) or vehicles were administered starting at gestational day (GD) 9.25, 9.5, or 9.75, a critical exposure time for inducing limb defects. Limb defects were examined at GD 17 using a dysmorphology scale based on abnormalities ranging from increased interdigital spacing to the deletion of multiple fingers and the ulna.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Alcohol treatment caused a high incidence of forelimb defects, particularly on the right side, that was higher in\n                      <jats:italic>\n                        Shh\n                        <jats:sup>+\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Gli2\n                        <jats:sup>+\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      fetuses compared to wild\u2010type fetuses. Dysmorphology scores were also significantly higher in the\n                      <jats:italic>\n                        Shh\n                        <jats:sup>+\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Gli2\n                        <jats:sup>+\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results extend previous findings demonstrating enhanced sensitivity to PAE\u2010induced craniofacial dysmorphology and support the hypothesis that genetic alterations in the Shh signaling pathway influences the vulnerability to alcohol\u2010induced birth defects. Moreover, these results emphasize the importance of understanding the interactions between genes and prenatal exposure to alcohol or other teratogens. Birth Defects Research 109:860\u2013865, 2017. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.1026","type":"journal-article","created":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T06:26:59Z","timestamp":1494829619000},"page":"860-865","source":"Crossref","is-referenced-by-count":19,"title":["Genetic vulnerabilities to prenatal alcohol exposure: Limb defects in sonic hedgehog and GLI2 heterozygous mice"],"prefix":"10.1002","volume":"109","author":[{"given":"Eric W.","family":"Fish","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura B.","family":"Murdaugh","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen K.","family":"Sulik","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina"},{"name":"Department of Cell Biology and Physiology University of North Carolina Chapel Hill North Carolina"},{"name":"Carolina Institute for Developmental Disabilities University of North Carolina Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, BRITE Institute North Carolina Central University Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Parnell","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Chapel Hill North Carolina"},{"name":"Department of Cell Biology and Physiology University of North Carolina Chapel Hill North Carolina"},{"name":"Carolina Institute for Developmental Disabilities University of North Carolina Chapel Hill North 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