title: Commonality in Down and fetal alcohol syndromes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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, Dyrk1a and Rcan1, 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 Ttc3 in DS embyros may influence nuclear pAkt localization and cell survival.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan Street, Indianapolis, IN 46202, USA.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Solzak
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Roper
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000097603:Dyrk Kinases
chemical_list: D002135:Calcium-Binding Proteins; D053148:Caspase 3; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C511512:DSCR1 protein, mouse
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