EMBRYONIC HEART AND SKIN DEFECTS IN MICE LACKING PLAKOGLOBIN

Plakoglobin is the only component common to both the desmosomal plaque and the cadherin-catenin cell adhesion complex in the adherens juncti on, It is highly homologous to vertebrate beta-catenin and to Drosophi la armadillo protein and may - like these proteins - be also involved in signaling pathways. To analyze the role of plakoglobin during mouse development we inactivated the plakoglobin gene by homologous recombi nation in embryonic stem cells and generated transgenic mice, Plakoglo bin null-mutant embryos died from Embryonic Day 10.5 onward, due to se vere heart defects. Some mutant embryos developed further, especially on a C57BL/6 genetic background, and died around birth, presumably due to cardiac dysfunction, and with skin blistering and subcorneal acant holysis. Ultrastructural analysis revealed that here desmosomes were g reatly reduced in number and structurally altered. Thus, using reverse d genetics we demonstrate that plakoglobin is an essential structural component for desmosome function, The skin phenotype in plakoglobin-de ficient mice is reminiscent of the human blistering disease, epidermol ytic hyperkeratosis. (C) 1996 Academic Press, Inc.