Postnatal lethality of P-cadherin/desmoglein 3 double knockout mice: demonstration of a cooperative effect of these cell adhesion molecules in tissue homeostasis of stratified squamous epithelia.
To investigate the cooperativity of different cell adhesion molecules in maintaining the structural integrity of the epidermis, we have generated mice deficient for both a classical cadherin, P-cadherin, and a desmosomal cadherin, desmoglein 3. In epithelial cells, P-cadherin is localized to the adherens junction, whereas desmoglein 3 is found in desmosomes. Previous studies have shown that these two junctional complexes are important for keratinocyte cell-cell adhesion. Both P-cadherin and desmoglein 3 expression are restricted to the basal and most immediate suprabasal cells of the epidermis, whereas both proteins are found throughout the oral mucosal epithelium. Although P-cadherin mutant mice have no apparent defect in epithelial cell adhesion, the desmoglein 3 mutant phenotype resembles that of patients with the autoimmune disease pemphigus vulgaris, in that the mice develop spontaneous mucous membrane blisters and trauma-induced skin blisters. The oral lesions in DSG3-/- mice reduce their food intake, resulting in a runted phenotype; however, most animals recover and live past weaning age. In contrast, animals mutant for both P-cadherin and desmoglein 3 die before weaning. The majority of the double mutant animals die around 1 wk after birth, apparently due to malnutrition. These studies suggest that loss of P-cadherin leads to a more severe desmoglein 3 mutant phenotype in the double knockout mice. This is the first in vivo evidence of possible synergism between a classical and desmosomal cadherin.
Lenox
J M
JM
Center for Research on Reproduction and Women's Health and Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Koch
P J
PJ
Mahoney
M G
MG
Lieberman
M
M
Stanley
J R
JR
Radice
G L
GL
D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051184:Desmoglein 3; D004817:Epidermis / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D007774:Lactation; D051379:Mice; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000737:chemistry
D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3