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
| Autor: | Peter Koch, Glenn L. Radice, John R. Stanley, Jennifer M. Lenox, Melanie Kirshenbaum Lieberman, My G. Mahoney |
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| Rok vydání: | 2000 |
| Předmět: |
Pathology
medicine.medical_specialty pemphigus vulgaris Dermatology Biology adherens junction Biochemistry Adherens junction Mice Desmosome medicine Animals Homeostasis Lactation education Molecular Biology Tissue homeostasis Mice Knockout education.field_of_study oral mucosa Desmoglein 3 integumentary system Cadherin Cell adhesion molecule Pemphigus vulgaris Mouth Mucosa Cell Biology Cadherins medicine.disease Cell biology medicine.anatomical_structure Animals Newborn Female desmosome Epidermis Keratinocyte |
| Zdroj: | Journal of Investigative Dermatology. 114:948-952 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2000.00976.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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