title: Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice.
abstract: Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an approximately 7 Mb 'cardiac critical region' in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease.
authors: Division of Pediatric Cardiology, Department of Pediatrics/Rady Children's Hospital of San Diego, USA.
authors: Maoqing
authors: M
authors: Ye
authors: Chris
authors: C
authors: Coldren
authors: Xingqun
authors: X
authors: Liang
authors: Teresa
authors: T
authors: Mattina
authors: Elizabeth
authors: E
authors: Goldmuntz
authors: D Woodrow
authors: DW
authors: Benson
authors: Dunbar
authors: D
authors: Ivy
authors: M B
authors: MB
authors: Perryman
authors: Lee Ann
authors: LA
authors: Garrett-Sinha
authors: Paul
authors: P
authors: Grossfeld
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D017353:Gene Deletion; D006345:Heart Septal Defects, Ventricular / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D006352:Heart Ventricles / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D006801:Humans; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D050784:Proto-Oncogene Protein c-ets-1