English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the zaia usage as premium feature

ZAIA

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the access of premium content as premium feature

Premium Content

Zendy Tools

Zendy Open

Cumulative evidence suggests that Hirschsprung disease (HSCR) is the consequence of multiple gene interactions that modulate the ability of enteric neural crest (NC) cells to populate the developing gut. One of the essential genes for this process is the NC transcription factor  Sox10 .  Sox10   Dom   mice on a mixed genetic background show variation in penetrance and expressivity of enteric aganglionosis that are analogous to the variable aganglionosis seen in human HSCR families. The phenotype of  Sox10   Dom   mice in congenic lines indicates this variation arises from modifiers in the genetic background. To determine whether known HSCR susceptibility loci are acting as modifiers of  Sox10 , we tested for association between genes in the endothelin signaling pathway ( EdnrB ,  Edn3 ,  Ece1 ) and severity of aganglionosis in an extended pedigree of B6C3FeLe. Sox10   Dom   mice. Single locus association analysis in this pedigree identifies interaction between  EdnrB  and  Sox10 . Additional analysis of F2 intercross progeny confirms a highly significant effect of  EdnrB  alleles on the  Sox10   Dom /+  phenotype. The presence of C57BL/6J alleles at  EdnrB  is associated with increased penetrance and more severe aganglionosis in  Sox10   Dom   mutants. Crosses between  EdnrB  and  Sox10  mutants corroborate this gene interaction with double mutant progeny exhibiting significantly more severe aganglionosis. The background strain of the  EdnrB  mutant further influences the phenotype of  Sox10 / EdnrB  double mutant progeny implying the action of additional modifiers on this phenotype. Our data demonstrates that  Sox10 – EdnrB  interactions can influence development of the enteric nervous system in mouse models and suggests that this interaction could contribute to the epistatic network producing variation between patients with aganglionosis.

Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10 Dom mouse model of Hirschsprung disease