title: Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies.
abstract: The Down syndrome critical region 1 (DSCR1) gene is located in syntenic regions of human chromosome 21 and mouse chromosome 16 and encodes a regulatory protein in the calcineurin/NFAT pathway. DSCR1 expression in the embryonic brain, craniofacial structures, and heart is consistent with a role in contributing to Down syndrome developmental anomalies. In the trisomy 16 (Ts16) murine model of Down syndrome, expression of DSCR1 isoforms is elevated and NFAT transcriptional activity is decreased in the developing heart and brain. The individual contribution of DSCR1 to Down syndrome-related anomalies was examined by specific restoration of DSCR1 to disomic levels in Ts16 embryos. However, genetic restoration of DSCR1 did not rescue major morphological abnormalities in cardiac or craniofacial development. These data demonstrate that trisomy of DSCR1 alone does not significantly contribute to developmental defects in Ts16 mice and underscore the complexity of developmental anomalies associated with Down syndrome.
authors.affiliation: Division of Molecular Cardiovascular Biology, Children's Medical Center Cincinnati, Cincinnati, Ohio 45229, USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Lange
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Rothermel
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Yutzey
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004171:Diploidy; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000196:embryology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014314:Trisomy / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; C108612:RCAN1 protein, human; D014157:Transcription Factors