Induction of sweat glands by epidermal growth factor in murine X-linked anhidrotic ectodermal dysplasia

Tabby (Ta), a murine X-linked mutant gene, produces a syndrome of ectodermal dysplasia including anhidrosis (absence of sweat glands). Development of sweat glands is related to that of dermal ridges (dermatoglyphics) and abnormal ridges may be associated with absence of sweat glands in the human syndrome of hypohidrotic ectodermal dysplasia (HED). We have found that dermal ridges occur in normal mice but are lacking in Ta mutants. Previously we showed that epidermal growth factor (EGF) reverses delayed eyelid opening and incisor eruption in Ta mice. We now report that EGF induces development of dermal ridges and functional sweat glands in Ta/Y hemizygotes, indicating a role in mammalian morphogenesis. Ta seems to be genetically homologous to human X-linked HED, as Ta maps close to loci homologous to linkage markers of HED and the two syndromes share many traits, including absence of all or most sweat glands. Absence of these glands causes hyperpyrexia, a clinical emergency in infants with HED; reversal of the trait in the mouse homologue of the disease indicates that an important genetically determined congenital defect in humans may become treatable.