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Generation and Characterization of Function Blocking Anti-Ectodysplasin A (EDA) Monoclonal Antibodies that Induce Ectodermal Dysplasia

Research output: Contribution to journalArticle

  • Christine Kowalczyk-Quintas
  • Laure Willen
  • Anh Thu Dang
  • Heidi Sarrasin
  • Aubry Tardivel
  • Katharina Hermes
  • Holm Schneider
  • Olivier Gaide
  • Olivier Donzé
  • Neil Kirby
  • Denis J Headon
  • Pascal Schneider

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)4273-4285
JournalJournal of Biological Chemistry
Issue number7
Early online date3 Jan 2014
Publication statusPublished - 3 Jan 2014


Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA-blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and post-developmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

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