Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice

• Published in: American journal of medical genetics. Part A 2009-07, Vol.149A (7), p.1438-1443
• Main Authors: Ye, Maoqing, Hamzeh, Rabih, Geddis, Amy, Varki, Nissi, Perryman, M. Benjamin, Grossfeld, Paul
• Format: Article
• Language: English
• Subjects: 11q deletion; Adult; Animals; Biological and medical sciences; Cardiology. Vascular system; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; Chromosomes, Human, Pair 11; Congenital heart diseases. Malformations of the aorta, pulmonary vessels and vena cava; Disease Models, Animal; Female; Gene Deletion; Heart; Heart - embryology; Heart - physiology; Heart Defects, Congenital - complications; Heart Defects, Congenital - genetics; Humans; hypoplastic left heart; Infant, Newborn; Jacobsen Distal 11q Deletion Syndrome - complications; Jacobsen Distal 11q Deletion Syndrome - genetics; Jacobsen syndrome; JAM-3; Male; Medical genetics; Medical sciences; Mice; Mice, Knockout; mouse model; Phenotype; Pregnancy; Thrombocytopenia, Neonatal Alloimmune - genetics; Young Adult
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32913

The 11q terminal deletion disorder (11q‐) is a rare chromosomal disorder caused by a deletion in distal 11q. Fifty‐six percent of patients have clinically significant congenital heart defects. A cardiac “critical region” has been identified in distal 11q that contains over 40 annotated genes. In this study, we identify the distal breakpoint of a patient with a paracentric inversion in distal 11q who had hypoplastic left heart and congenital thrombocytopenia. The distal breakpoint mapped to JAM‐3, a gene previously identified as a candidate gene for causing HLHS in 11q‐. To determine the role of JAM‐3 in cardiac development, we performed a comprehensive cardiac phenotypic assessment in which the mouse homolog for JAM‐3, JAM‐C, has been deleted. These mice have normal cardiac structure and function, indicating that haplo‐insufficiency of JAM‐3 is unlikely to cause the congenital heart defects that occur in 11q‐ patients. Notably, we identified a previously undescribed phenotype, jitteriness, in most of the sick or dying adult JAM‐C knockout mice. These data provide further insights into the identification of the putative disease‐causing cardiac gene(s) in distal 11q, as well as the functions of JAM‐C in normal organ development. © 2009 Wiley‐Liss, Inc.