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 (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.
Max Delbrueck Center for Molecular Medicine (MDC), D-13092 Berlin, Germany.
Katja S
KS
Grossmann
Christine
C
Grund
Joerg
J
Huelsken
Martin
M
Behrend
Bettina
B
Erdmann
Werner W
WW
Franke
Walter
W
Birchmeier
D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D003433:Crosses, Genetic; D003902:Detergents / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D006321:Heart / Q000196:embryology* / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008957:Models, Genetic; D009154:Mutation; D017830:Octoxynol / Q000494:pharmacology; D010641:Phenotype; D051191:Plakophilins; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors
D003902:Detergents; C495338:Pkp2 protein, mouse; D051191:Plakophilins; D011506:Proteins; D017830:Octoxynol