Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice.
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.
Ye
Maoqing
M
Department of Pediatrics, Division of Cardiology, UCSD School of Medicine, San Diego, California, USA.
Hamzeh
Rabih
R
Geddis
Amy
A
Varki
Nissi
N
Perryman
M Benjamin
MB
Grossfeld
Paul
P
D000328:Adult; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D002880:Chromosomes, Human, Pair 11; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006321:Heart / Q000196:embryology / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000150:complications / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000235:genetics; D055815:Young Adult
D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human