Requirement of Plakophilin 2 for Heart Morphogenesis and Cardiac Junction Formation
Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease. We have ablated the plakophilin 2 gene in mice. The resulting mutant mice exhibit lethal alterations in heart morphogenesis and stability at mid-gestation (E...
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Published in | The Journal of cell biology Vol. 167; no. 1; pp. 149 - 160 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Rockefeller University Press
11.10.2004
The Rockefeller University Press |
Subjects | |
Online Access | Get full text |
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Summary: | Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease. We have ablated the plakophilin 2 gene in mice. The resulting mutant mice exhibit lethal alterations in heart morphogenesis and stability at mid-gestation (E10.5-E11), characterized by reduced trabeculation, disarrayed cytoskeleton, ruptures of cardiac walls, and blood leakage into the pericardiac cavity. In the absence of plakophilin 2, the cytoskeletal linker protein desmoplakin dissociates from the plaques of the adhering junctions that connect the cardiomyocytes and forms granular aggregates in the cytoplasm. By contrast, embryonic epithelia show normal junctions. Thus, we conclude that plakophilin 2 is important for the assembly of junctional proteins and represents an essential morphogenic factor and architectural component of the heart. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Correspondence to Walter Birchmeier: wbirch@mdc-berlin.de J. Huelsken's present address is ISREC, CH-1066 Lausanne, Switzerland. Abbreviations used in this paper: ES, embryonic stem; IF, intermediate-sized filament; wt, wild-type. M. Behrend's present address is Franz Volhard Clinic, D-13125 Berlin, Germany. |
ISSN: | 0021-9525 1540-8140 |
DOI: | 10.1083/jcb.200402096 |