title: 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.
abstract: 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.
authors.affiliation: Center for Research on Reproduction and Women's Health and Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Lenox
authors.forename: P J
authors.initials: PJ
authors.lastname: Koch
authors.forename: M G
authors.initials: MG
authors.lastname: Mahoney
authors.forename: M
authors.initials: M
authors.lastname: Lieberman
authors.forename: J R
authors.initials: JR
authors.lastname: Stanley
authors.forename: G L
authors.initials: GL
authors.lastname: Radice
mesh_terms: 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
chemical_list: D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3