Commonality in Down and fetal alcohol syndromes. Issue 4 (3rd April 2013)

• Record Type: Journal Article
• Authors: Solzak, Jeffrey P.; Liang, Yun; Zhou, Feng C.; Roper, Randall J.
• Is Part Of: Birth defects research. Volume 97:Issue 4(2013:Apr.)
• Page Start: 187
• Page End: 197
• Publication Date: 2013-04-03
• Subjects: Teratology -- Periodicals; Abnormalities, Human -- Research -- Periodicals; Abnormalities, Human -- Periodicals; 616.043
• DOI: 10.1002/bdra.23129
• Languages: English
• ISSNs: 1542-0752

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bdra23129-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Down syndrome (DS) and Fetal Alcohol Syndrome (FAS) are two leading causes of birth defects with phenotypes ranging from craniofacial abnormalities to cognitive impairment. Despite different origins, we report that in addition to sharing many phenotypes, DS and FAS may have common underlying mechanisms of development.</p> </sec> <sec id="bdra23129-sec-0002" sec-type="section"> <title>METHODS</title> <p>Literature was surveyed for DS and FAS as well as mouse models. Gene expression and apoptosis were compared in embryonic mouse models of DS and FAS by qPCR, immunohistochemical and immunoflurorescence analyses. The craniometry was examined using MicroCT at postnatal day 21.</p> </sec> <sec id="bdra23129-sec-0003" sec-type="section"> <title>RESULTS</title> <p>A literature survey revealed over 20 comparable craniofacial and structural deficits in both humans with DS and FAS and corresponding mouse models. Similar phenotypes were experimentally found in pre‐ and postnatal craniofacial and neurological tissues of DS and FAS mice. Dysregulation of two genes, <italic>Dyrk1a</italic> and <italic>Rcan1</italic>, key to craniofacial and neurological precursors of DS, was shared in craniofacial precursors of DS and FAS embryos. Increased cleaved caspase 3 expression was also discovered in comparable regions of the craniofacial and brain precursors of DS and FAS embryos. Further mechanistic studies suggested overexpression of trisomic <italic>Ttc3</italic> in DS embyros may influence nuclear pAkt localization and cell survival.</p> </sec> <sec id="bdra23129-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>This first and initial study indicates that DS and FAS share common dysmorphologies in humans and animal models. This work also suggests common mechanisms at cellular and molecular levels that are disrupted by trisomy or alcohol consumption during pregnancy and lead to craniofacial and neurological phenotypes associated with DS or FAS. <italic>Birth Defects Research (Part A) 97:187–197, 2013</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>