06-P029 Congenital hypertelorism & osteopenia, a novel autosomal recessive disease of development

terized by ectodermal dysplasia (ED). The nectin-1 (N1) null mutant mice have a mild defect in skin, (Wakamatsu etal., 2007), but no severe phenotypes were reported, suggesting the compensation by other nectins. In this study, we tested this hypothesis by generating N1 and N3 compound mutant mice. We observed coexpression of N1 and N3 in the inner root sheath of hair follicles and in the suprabasal layer of epidermis. All compound mutants showed severe skin abnormality and reduced hair follicles at post natal day 10. Histological analysis indicated that the compound mutant skin was eosinophilic and the nuclei in the basal cell layer exhibited abnormal shapes and arrangement. Their hair follicles were smaller than wild type and had lost their typical structure. Immunohistochemical analysis revealed that the basal cell layer marker laminin, as well as filaggrin and loricrin were severely reduced in the mutant skin, and that keratin14 was reduced while the expression keratin 10 was normal. The cell junction molecules E-cadherin, ZO-1, and DSG were reduced or mislocalized, and the expression of p63 and Ki67 were severely reduced in the mutant skin. Similar gene expression alterations were also observed in the mutant hair follicles. These results indicate that N1 and N3 have important functions in the control of epidermal homeostasis and hair formation and that they are functionally redundant in these processes.