Patients with defective ectodysplasin A (EDA) are affected by X-linked hypohidrotic
ectodermal dysplasia (XLHED), a condition characterized by sparse hair, inability
to sweat, decreased lacrimation, frequent pulmonary infections, and missing and malformed
teeth. The canine model of XLHED was used to study the developmental impact of EDA
on secondary dentition, since dogs have an entirely brachyodont, diphyodont dentition
similar to that in humans, as opposed to mice, which have only permanent teeth (monophyodont
dentition), some of which are very different (aradicular hypsodont) than brachyodont
human teeth. Also, clinical signs in humans and dogs with XLHED are virtually identical,
whereas several are missing in the murine equivalent. In our model, the genetically
missing EDA was compensated for by postnatal intravenous administration of soluble
recombinant EDA. Untreated XLHED dogs have an incomplete set of conically shaped teeth
similar to those seen in human patients with XLHED. After treatment with EDA, significant
normalization of adult teeth was achieved in four of five XLHED dogs. Moreover, treatment
restored normal lacrimation and resistance to eye and airway infections and improved
sweating ability. These results not only provide proof of concept for a potential
treatment of this orphan disease but also demonstrate an essential role of EDA in
the development of secondary dentition.