How to cite this article: Ye M, Hamzeh R, Geddis A, Varki N, Perryman MB, Grossfeld P. 2009. Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice. Am J Med Genet Part A 149A:1438–1443.
Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice†
Article first published online: 16 JUN 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 7, pages 1438–1443, July 2009
How to Cite
Ye, M., Hamzeh, R., Geddis, A., Varki, N., Perryman, M. B. and Grossfeld, P. (2009), Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice. Am. J. Med. Genet., 149A: 1438–1443. doi: 10.1002/ajmg.a.32913
- Issue published online: 18 JUN 2009
- Article first published online: 16 JUN 2009
- Manuscript Accepted: 5 APR 2009
- Manuscript Received: 10 FEB 2009
- NIH. Grant Number: KO8 HL70640-02
- State of South Dakota. Grant Number: 2010
- Jacobsen syndrome;
- hypoplastic left heart;
- mouse model;
- 11q deletion
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.