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.