RGD Reference Report - Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations. - Rat Genome Database

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Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations.

Authors: Dang, R  Torigoe, D  Suzuki, S  Kikkawa, Y  Moritoh, K  Sasaki, N  Agui, T 
Citation: Dang R, etal., PLoS One. 2011;6(9):e24086. Epub 2011 Sep 7.
RGD ID: 6480217
Pubmed: PMID:21915282   (View Abstract at PubMed)
PMCID: PMC3168492   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0024086   (Journal Full-text)

Hirschsprung disease (HSCR) is thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. However, it remains unknown whether the single complete deletion of important HSCR-associated genes is sufficient to result in HSCR disease. In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrb(sl) mutations. Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4). Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. We found that the same genetic background markedly changed the aganglionosis, but resulted in only slight changes to hearing loss and pigment disorder. This provided the important evidence, in support of previous studies, that different lineages of neural crest-derived cells migrating along with various pathways are regulated by different signal molecules. This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Ednrb  (endothelin receptor type B)
Ednrbsl  (endothelin receptor type B, spotting lethal)

Genes (Mus musculus)
Ednrb  (endothelin receptor type B)

Genes (Homo sapiens)
EDNRB  (endothelin receptor type B)

QTLs
Gdil1  (Gastrointestinal dilation QTL 1)

Strains
AR-Ednrbsl/Hkv  (Aganglionosis rat)
F344.AR-Ednrbsl/Hkv  (Aganglionosis rat)
LE/Hkv.AR-Ednrbsl  (Aganglionosis rat)


Additional Information