Desmoglein isoform distribution affects stratum corneum structure and function.
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.
Elias
P M
PM
Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.
Matsuyoshi
N
N
Wu
H
H
Lin
C
C
Wang
Z H
ZH
Brown
B E
BE
Stanley
J R
JR
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D051184:Desmoglein 3; D003896:Desmosomes / Q000378:metabolism / Q000648:ultrastructure; D004817:Epidermis / Q000378:metabolism / Q000648:ultrastructure*; D000091344:Filaggrin Proteins; D015151:Immunoblotting; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000033:anatomy & histology / Q000378:metabolism; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D014870:Water Loss, Insensible / Q000502:physiology*
D015820:Cadherins; D015815:Cell Adhesion Molecules; C071894:DSG3 protein, human; D051184:Desmoglein 3; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D010455:Peptides; D020033:Protein Isoforms; D011498:Protein Precursors; C064554:loricrin; C032253:involucrin; C085706:FLAG peptide