title: Gene-targeted deletion of OPCML and Neurotrimin in mice does not yield congenital heart defects.
abstract: Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal11q. Many of the most common and severe congenital heart defects that occur in the general population occur in 11q-. Previous studies have demonstrated that gene-targeted deletion in mice of ETS-1, a cardiac transcription factor in distal 11q, causes ventricular septal defects with 100% penetrance. It is unclear whether deletion of other genes in distal 11q contributes to the full spectrum of congenital heart defects that occur in 11q-. Three patients with congenital heart defects have been identified that carry a translocation or paracentric inversion with a breakpoint in distal 11q disrupting one of two functionally related genes, OPCML and Neurotrimin. OPCML and Neurotrimin are two members of the IgLON subfamily of cell adhesion molecules. In this study, we report the generation and cardiac phenotype of single and double heterozygous gene-targeted OPCML and Neurotrimin knockout mice. No cardiac phenotype was detected, consistent with a single gene model as the cause of the congenital heart defects in 11q-.
authors.affiliation: Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Pediatrics, UCSD School of Medicine, San Diego, California.
authors.forename: Maoqing
authors.initials: M
authors.lastname: Ye
authors.forename: Fabienne
authors.initials: F
authors.lastname: Parente
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: M Benjamin
authors.initials: MB
authors.lastname: Perryman
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Grossfeld
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D058851:GPI-Linked Proteins / Q000235:genetics; D017353:Gene Deletion; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D010641:Phenotype; D014178:Translocation, Genetic
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D019006:Neural Cell Adhesion Molecules; C059785:OPCML protein, human; C092530:neurotrimin
keywords: Jacobsen syndrome; Neurotrimin; OPCML; congenital heart disease; mouse knockout