Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice. Hum Mol Genet 2010 Feb 15;19(4):648-56
Date
11/28/2009Pubmed ID
19942620Pubmed Central ID
PMC2807373DOI
10.1093/hmg/ddp532Scopus ID
2-s2.0-77950364003 (requires institutional sign-in at Scopus site) 118 CitationsAbstract
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.
Author List
Ye M, Coldren C, Liang X, Mattina T, Goldmuntz E, Benson DW, Ivy D, Perryman MB, Garrett-Sinha LA, Grossfeld PMESH terms used to index this publication - Major topics in bold
AnimalsChromosome Deletion
Chromosome Mapping
Chromosomes, Human, Pair 11
Gene Deletion
Heart Septal Defects, Ventricular
Heart Ventricles
Humans
Jacobsen Distal 11q Deletion Syndrome
Mice
Mice, Inbred C57BL
Mice, Knockout
Proto-Oncogene Protein c-ets-1
