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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EDARADDHumanhypohidrotic ectodermal dysplasia  ISOEdaradd (Rattus norvegicus)DNA:missense mutation:exon:p.Pro153Ser(rat)RGD 
EdaraddMousehypohidrotic ectodermal dysplasia  ISOEdaradd (Rattus norvegicus)DNA:missense mutation:exon:p.Pro153Ser(rat)RGD 
EdaraddRathypohidrotic ectodermal dysplasia  IAGP DNA:missense mutation:exon:p.Pro153Ser(rat)RGD 
EdaraddswhKyoRathypohidrotic ectodermal dysplasia  IAGP  RGD 
WTC-swh/KyoRathypohidrotic ectodermal dysplasia  IAGP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EdaraddRatpositive regulation of non-canonical NF-kappaB signal transduction  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EdaraddRatabnormal awl hair morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatabnormal awl hair morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatabnormal awl hair morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddRatabnormal mammary gland alveolus morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatabnormal mammary gland alveolus morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatabnormal mammary gland alveolus morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddRatabnormal molar cusp morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatabnormal molar cusp morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatabnormal molar cusp morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddRatabnormal tongue morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatabnormal tongue morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatabnormal tongue morphology  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddRatabsent Meibomian glands  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatabsent Meibomian glands  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatabsent Meibomian glands  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddRatabsent sweat gland  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatabsent sweat gland  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatabsent sweat gland  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddRatsmall male preputial gland  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
EdaraddswhKyoRatsmall male preputial gland  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
WTC-swh/KyoRatsmall male preputial gland  IAGP DNA:missense mutation:exon:p.Pro153SerratRGD 
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