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

J Invest Dermatol. 2000 May;114(5):948-52. doi: 10.1046/j.1523-1747.2000.00976.x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cadherins / analysis
  • Cadherins / genetics
  • Cadherins / physiology*
  • Desmoglein 3
  • Epidermis / physiology*
  • Female
  • Homeostasis*
  • Lactation
  • Mice
  • Mice, Knockout
  • Mouth Mucosa / chemistry

Substances

  • Cadherins
  • DSG3 protein, human
  • Desmoglein 3