title: Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart.
abstract: Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a constituent of the cytoplasmic plaque of desmosomes as well as of other adhering cell junctions, and is involved in anchorage of cytoskeletal filaments to specific cadherins. We have generated a null mutation of the plakoglobin gene in mice. Homozygous -/- mutant animals die between days 12-16 of embryogenesis due to defects in heart function. Often, heart ventricles burst and blood floods the pericard. This tissue instability correlates with the absence of desmosomes in heart, but not in epithelia organs. Instead, extended adherens junctions are formed in the heart, which contain desmosomal proteins, i.e., desmoplakin. Thus, plakoglobin is an essential component of myocardiac desmosomes and seems to play a crucial role in the sorting out of desmosomal and adherens junction components, and consequently in the architecture of intercalated discs and the stabilization of heart tissue.
authors.affiliation: Max-Delbruck-Center for Molecular Medicine, Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: V
authors.initials: V
authors.lastname: Brinkmann
authors.forename: B
authors.initials: B
authors.lastname: Ledermann
authors.forename: M
authors.initials: M
authors.lastname: Behrend
authors.forename: C
authors.initials: C
authors.lastname: Grund
authors.forename: C
authors.initials: C
authors.lastname: Thalhammer
authors.forename: F
authors.initials: F
authors.lastname: Vogel
authors.forename: C
authors.initials: C
authors.lastname: Birchmeier
authors.forename: U
authors.initials: U
authors.lastname: Günthert
authors.forename: W W
authors.initials: WW
authors.lastname: Franke
authors.forename: W
authors.initials: W
authors.lastname: Birchmeier
mesh_terms: D000818:Animals; D015820:Cadherins; D015815:Cell Adhesion Molecules / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051180:Desmoplakins; D003896:Desmosomes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry; D005822:Genetic Vectors / Q000235:genetics; D006321:Heart / Q000196:embryology* / Q000502:physiology; D007365:Intercellular Junctions / Q000737:chemistry; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009206:Myocardium / Q000737:chemistry / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; C489083:Cdh2 protein, mouse; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495295:Dsp protein, mouse; C495293:Jup protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin