QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online August 3, 2005
doi: 10.1242/10.1242/jcs.02476

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dorner, A. A. Articles by Vestweber, D. Search for Related Content PubMed PubMed Citation Articles by Dorner, A. A. Articles by Vestweber, D.

Coxsackievirus-adenovirus receptor (CAR) is essential for early embryonic cardiac development

Armin A. Dorner^1,*, Frank Wegmann^2,*, Stefan Butz², Karen Wolburg-Buchholz³, Hartwig Wolburg³, Andreas Mack³, Ines Nasdala², Benjamin August², Jürgen Westermann⁴, Fritz G. Rathjen¹ and Dietmar Vestweber^2,5,

¹ Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Robert-Rössie-Straße10, 13125 Berlin, Germany
² Institute of Cell Biology, ZMBE, University of Münster, 48149 Bad Nauheim, Germany
³ Institute of Pathology, University of Tübingen, Wilhelmstr. 7, 72074 Tübingen, Germany
⁴ Institute of Anatomy, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
⁵ Max-Planck-Institute of Molecular Biomedicine, Von-Esmarch-Straße 56, 48149 Münster, Germany

Author for correspondence (e-mail: vestweb{at}uni-muenster.de)

Accepted 9 May 2005

The coxsackievirus-adenovirus receptor (CAR) is a cell contact protein on various cell types with unknown physiological function. It belongs to a subfamily of the immunoglobulin-superfamily of which some members are junctional adhesion molecules on epithelial and/or endothelial cells. CAR is dominantly expressed in the hearts and brains of mice until the newborne phase after which it becomes mainly restricted to various epithelial cells. To understand more about the physiological function of CAR, we have generated CAR-deficient mice by gene targeting. We found that these mice die between E11.5 and E13.5 of embryonal development. Ultrastructural analysis of cardiomyocytes revealed that the density of myofibrils was reduced and that their orientation and bundling was disorganized. In addition, mitochondria were enlarged and glycogen storage strongly enriched. In line with these defects, we observed pericardial edema formation as a clear sign of insufficient heart function. Developmental abnormalities likely to be secondary effects of gene ablation were the persistent singular cardial atrio-ventricular canal and dilatations of larger blood vessels such as the cardinal veins. The secondary nature of these defects was supported by the fact that CAR was not expressed on vascular cells or on cells of the vascular wall. No obvious signs for alterations of the histological organization of the placenta were observed. We conclude that CAR is required for embryonal heart development, most likely due to its function during the organization of myofibrils in cardiomyocytes.

Key words: Cardiomyocytes, Junctions, Heart development, Junctional adhesion molecules, Cell adhesion

This article has been cited by other articles:

				U. Lisewski, Y. Shi, U. Wrackmeyer, R. Fischer, C. Chen, A. Schirdewan, R. Juttner, F. Rathjen, W. Poller, M. H. Radke, et al. The tight junction protein CAR regulates cardiac conduction and cell-cell communication J. Exp. Med., September 29, 2008; 205(10): 2369 - 2379. [Abstract] [Full Text] [PDF]

				M. Mirza, C. Petersen, K. Nordqvist, and K. Sollerbrant Coxsackievirus and Adenovirus Receptor Is Up-Regulated in Migratory Germ Cells during Passage of the Blood-Testis Barrier Endocrinology, November 1, 2007; 148(11): 5459 - 5469. [Abstract] [Full Text] [PDF]

				M. G. Bixel, B. Petri, A. G. Khandoga, A. Khandoga, K. Wolburg-Buchholz, H. Wolburg, S. Marz, F. Krombach, and D. Vestweber A CD99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo Blood, June 15, 2007; 109(12): 5327 - 5336. [Abstract] [Full Text] [PDF]

				S. Baumer, L. Keller, A. Holtmann, R. Funke, B. August, A. Gamp, H. Wolburg, K. Wolburg-Buchholz, U. Deutsch, and D. Vestweber Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development Blood, June 15, 2006; 107(12): 4754 - 4762. [Abstract] [Full Text] [PDF]

				J.-W. Chen, B. Zhou, Q.-C. Yu, S. J. Shin, K. Jiao, M. D. Schneider, H. S. Baldwin, and J. M. Bergelson Cardiomyocyte-Specific Deletion of the Coxsackievirus and Adenovirus Receptor Results in Hyperplasia of the Embryonic Left Ventricle and Abnormalities of Sinuatrial Valves Circ. Res., April 14, 2006; 98(7): 923 - 930. [Abstract] [Full Text] [PDF]

				D. Asher, R. Finberg, F. Wegmann, S. Butz, F. G. Rathjen, K. Wolburg-Buchholz, H. Wolburg, and D. Vestweber CAR might provide a survival signal for myocardial cells J. Cell Sci., December 15, 2005; 118(24): 5679 - 5680. [Full Text] [PDF]