TARGETED MUTATION OF PLAKOGLOBIN IN MICE REVEALS ESSENTIAL FUNCTIONS OF DESMOSOMES IN THE EMBRYONIC HEART

Plakoglobin (gamma-catenin), a member of the armadillo family of prote ins, 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 anima ls die between days 12-16 of embryogenesis due to defects in heart fun ction. Often, heart ventricles burst and blood floods the pericard. Th is tissue instability correlates with the absence of desmosomes in hea rt, but not in epithelial organs. Instead, extended adherens junctions are formed in the heart, which contain desmosomal proteins, i.e., des moplakin. Thus, plakoglobin is an essential component of myocardiac de smosomes and seems to play a crucial role in the sorting out of desmos omal and adherens junction components, and consequently in the archite cture of intercalated discs and the stabilization of heart tissue.