Cooperation of Nectin-1 and Nectin-3 Is Required for Maintenance of Epidermal Stratification and Proper Hair Shaft Formation in the Mouse

Abstract

Nectins constitute a family of four cell adhesion molecules which are localized on cell membrane. Mutations in NECTIN-1 gene cause the human ectodermal dysplasia syndrome (CLPED1) manifesting severe defects in skin and its appendages. However, nectin-1 null mutant mice have only a mild defect in epidermal stratification suggesting compensation by other nectins. We have analysed the epidermal and hair phenotypes of nectin-1; nectin-3 compound mutants. Epidermis was fragile and displayed severe defects in stratification, hair follicles were hypoplastic, and hair shaft structure was abnormal. Immunohistochemical analysis revealed severe defects in cell-cell junctions including adherens and tight junctions as well as desmosomes. It is therefore likely that the phenotypes were caused by impaired cell adhesion. The expression patterns of nectin-1 and nectin-3 together with the phenotypes in compound mutants indicated that heterophilic interactions between the two nectins are required for proper formation of epidermis and hair in mice. The nectin-1; nectin-3 compound mutant mice partially reproduced the phenotype of human CLPED1 patients.