Gene defect in ectodermal dysplasia implicates a death domain adapter in development

D. J. Headon, S. A. Emmal, Betsy Ferguson, A. S. Tucker, M. J. Justice, P. T. Sharpe, Jonathan (Jon) Zonana, P. A. Overbeek

Research output: Contribution to journalArticle

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Abstract

Members of the tumour-necrosis factor receptor (TNFR) family that contain an intracellular death domain initiate signalling by recruiting cytoplasmic death domain adapter proteins. Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives. Mutations in Edar - or its ligand, Eda - cause hypohidrotic ectodermal dysplasia in humans and mice. This disorder is characterized by sparse hair, a lack of sweat glands and malformation of teeth. Here we report the identification of a death domain adapter encoded by the mouse crinkled locus. The crinkled mutant has an hypohidrotic ectodermal dysplasia phenotype identical to that of the edar (downless) and eda (Tabby) mutants. This adapter, which we have called Edaradd (for Edar-associated death domain), interacts with the death domain of Edar and links the receptor to downstream signalling pathways. We also identify a missense mutation in its human orthologue, EDARADD, that is present in a family affected with hypohidrotic ectodermal dysplasia. Our findings show that the death receptor/adapter signalling mechanism is conserved in developmental, as well as apoptotic, signalling.

Original languageEnglish (US)
Pages (from-to)913-916
Number of pages4
JournalNature
Volume414
Issue number6866
DOIs
StatePublished - Dec 20 2001

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Ectodermal Dysplasia
Anhidrotic Ectodermal Dysplasia 1
Genes
Tumor Necrosis Factor Receptors
Edar Receptor
Hair
Tooth
Sweat Glands
Death Domain Receptors
Missense Mutation
Death Domain
Proteins
Ligands
Phenotype
Mutation

ASJC Scopus subject areas

  • General

Cite this

Headon, D. J., Emmal, S. A., Ferguson, B., Tucker, A. S., Justice, M. J., Sharpe, P. T., ... Overbeek, P. A. (2001). Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature, 414(6866), 913-916. https://doi.org/10.1038/414913a

Gene defect in ectodermal dysplasia implicates a death domain adapter in development. / Headon, D. J.; Emmal, S. A.; Ferguson, Betsy; Tucker, A. S.; Justice, M. J.; Sharpe, P. T.; Zonana, Jonathan (Jon); Overbeek, P. A.

In: Nature, Vol. 414, No. 6866, 20.12.2001, p. 913-916.

Research output: Contribution to journalArticle

Headon, DJ, Emmal, SA, Ferguson, B, Tucker, AS, Justice, MJ, Sharpe, PT, Zonana, JJ & Overbeek, PA 2001, 'Gene defect in ectodermal dysplasia implicates a death domain adapter in development', Nature, vol. 414, no. 6866, pp. 913-916. https://doi.org/10.1038/414913a
Headon DJ, Emmal SA, Ferguson B, Tucker AS, Justice MJ, Sharpe PT et al. Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature. 2001 Dec 20;414(6866):913-916. https://doi.org/10.1038/414913a
Headon, D. J. ; Emmal, S. A. ; Ferguson, Betsy ; Tucker, A. S. ; Justice, M. J. ; Sharpe, P. T. ; Zonana, Jonathan (Jon) ; Overbeek, P. A. / Gene defect in ectodermal dysplasia implicates a death domain adapter in development. In: Nature. 2001 ; Vol. 414, No. 6866. pp. 913-916.
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