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

被引:288
作者
Headon, DJ
Emmal, SA
Ferguson, BM
Tucker, AS
Justice, MJ
Sharpe, PT
Zonana, J
Overbeek, PA [1 ]
机构
[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[3] Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA
[4] Guys Hosp, Univ London Kings Coll, MRC, Ctr Dev Neurobiol, London SE1 1UL, England
[5] Guys Hosp, Univ London Kings Coll, GKT Dent Inst, Dept Craniofacial Dev, London SE1 9RT, England
基金
英国医学研究理事会;
关键词
D O I
10.1038/414913a
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Members of the tumour-necrosis factor receptor (TNFR) family that contain an intracellular death domain initiate signalling by recruiting cytoplasmic death domain adapter proteins(1,2). Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives(3,4). Mutations in Edar-or its ligand, Eda-cause hypohidrotic ectodermal dysplasia in humans and mice(3-7). This disorder is characterized by sparse hair, a lack of sweat glands and malformation of teeth(8). 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(9). 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.
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收藏
页码:913 / 916
页数:4
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