A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene.

• 庫本, 高志

• Yokoe, Mayuko

• Hashimoto, Ryoko

• Hiai, Hiroshi

• Serikawa, Tadao

抄録

[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.

収録刊行物

• BMC genetics

  BMC genetics 12 2011-10-21

  BioMed Central Ltd.

キーワード

• 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

詳細情報

• CRID: 1050564285690810496
• NII論文ID: 120004770244
• NII書誌ID: AA12034956
• ISSN: 14712156
• HANDLE: 2433/159720
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles