| First Author | Yan M | Year | 2002 |
| Journal | Curr Biol | Volume | 12 |
| Issue | 5 | Pages | 409-13 |
| PubMed ID | 11882293 | Mgi Jnum | J:75381 |
| Mgi Id | MGI:2176400 | Doi | 10.1016/s0960-9822(02)00687-5 |
| Citation | Yan M, et al. (2002) Identification of a Novel Death Domain-Containing Adaptor Molecule for Ectodysplasin-A Receptor that Is Mutated in crinkled Mice. Curr Biol 12(5):409-13 |
| abstractText | Hypohydrotic Ectodermal Dysplasia (HED) is a genetic disease seen in humans and mice. It is characterized by loss of hair, sweat glands, and teeth. The predominant X-linked form results from mutations in ectodysplasin-A (EDA), a TNF-like ligand. A phenotypically indistinguishable autosomal form of the disease results from mutations in the receptor for EDA (EDAR). EDAR is a NF-kappaB-activating, death domain-containing member of the TNF receptor family. crinkled, a distinct autosomal form of HED, was discovered in a mouse strain in which both the ligand (EDA) and receptor (EDAR) were wild-type, suggestive of a disruption further downstream in the signaling pathway. Employing a forward genetic approach, we have cloned crinkled (CR) and find it to encode a novel death domain-containing adaptor. crinkled binds EDAR through a homotypic death domain interaction and mediates engagement of the NF-kappaB pathway, possibly by recruiting TRAF2 to the receptor-signaling complex. This is an unprecedented example of naturally occurring mutations in ligand, receptor, or adaptor giving rise to the same phenotypic disease characterized by a defect in the proper development of epidermal appendages. |
