RGD Reference Report - A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene. - Rat Genome Database

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

Authors: Kuramoto, Takashi  Yokoe, Mayuko  Hashimoto, Ryoko  Hiai, Hiroshi  Serikawa, Tadao 
Citation: Kuramoto T, etal., BMC Genet. 2011 Oct 21;12:91. doi: 10.1186/1471-2156-12-91.
RGD ID: 14398762
Pubmed: PMID:22013926   (View Abstract at PubMed)
PMCID: PMC3224228   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2156-12-91   (Journal Full-text)

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.

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Edaradd  (EDAR associated via death domain)
EdaraddswhKyo  (EDAR-associated death domain;swh Kyo mutant)

Genes (Mus musculus)
Edaradd  (EDAR associated via death domain)

Genes (Homo sapiens)
EDARADD  (EDAR associated via death domain)

WTC-swh/Kyo  (NA)

Additional Information