Of more than 150 ectodermal dysplasias affecting skin and skin appendages, the X-linked anhidrotic ectodermal dysplasia (EDA) is the only one for which the gene involved has been identified. The gene encodes a protein, which we have named ectodysplasin-A, that has a single transmembrane region and a long, extracellular carboxyterminal tail. Because individuals with EDA have sparse hair, rudimentary teeth, and few sweat glands, the gene is likely involved at an early branch point in the interaction of mesenchyme and embryonic ectoderm during the development of skin appendages. Work in the last year has analyzed the gene and its transcripts, and has begun to give some hints of their mode of action. Analysis of the promoter region has revealed transcription elements that include a new type of enhancer, possibly implicated in the tissue specificity of the gene. Eight different transcripts, all beginning with the same first exon, have been identified. The longest contain a collagen-like repeat, suggesting a role for ectodysplasin-A in cell-cell or cell-matrix interactions. Consistent with this view, transfection of the gene into some types of cells leads to their detachment from substrate. In an additional approach, our collaborators have demonstrated that the Tabby mouse, which has many of the features observed in human EDA, results from the loss of function of the orthologous mouse gene. This provides an experimental system to study the function of the gene in embryonic development. - Ectodermal dysplasia; hair; sweat glands; teeth; anhidrotic; collagen-like repeats; enhancer; LEF-1; tabby mouse; transgene
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