論文 - 詳細
| RRC ID | 27755 |
|---|---|
| 著者 | Kuramoto T, Yokoe M, Hashimoto R, Hiai H, Serikawa T. |
| タイトル | A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene. |
| ジャーナル | BMC Genet |
| Abstract |
BACKGROUND:Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda), Eda receptor (Edar), and Edar-associated death domain (Edaradd), which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh). Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation. RESULTS:The swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB. CONCLUSIONS:These findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies. |
| 巻・号 | 12 |
| ページ | 91 |
| 公開日 | 2011-10-21 |
| DOI | 10.1186/1471-2156-12-91 |
| PII | 1471-2156-12-91 |
| PMID | 22013926 |
| PMC | PMC3224228 |
| MeSH | Animals Chromosome Mapping Disease Models, Animal Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / genetics* Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / pathology Edar-Associated Death Domain Protein / genetics* Edar-Associated Death Domain Protein / metabolism* HEK293 Cells Humans Hypohidrosis / genetics Mice Mutation, Missense / genetics NF-kappa B / genetics NF-kappa B / metabolism* Rats Sweat Glands / pathology |
| IF | 2.567 |
| 引用数 | 12 |
| WOS 分野 | GENETICS & HEREDITY |
| リソース情報 | |
| ラット | ACI/NKyo(strainID=6) WTC/Kyo(strainID=18) WTC-swh/Kyo(strainID=539) |