Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice.

ABSTRACT: Mutations in the RET gene are the primary cause of Hirschsprung disease (HSCR), or congenital intestinal aganglionosis. However, how RET malfunction leads to HSCR is not known. It has recently been shown that glial cell line-derived neurotrophic factor (GDNF) family receptor alpha1 (GFRalpha1), which binds to GDNF and activates RET, is essential for the survival of enteric neurons. In this study, we investigated Ret regulation of enteric neuron survival and its potential involvement in HSCR. Conditional ablation of Ret in postmigratory enteric neurons caused widespread neuronal death in the colon, which led to colonic aganglionosis. To further examine this finding, we generated a mouse model for HSCR by reducing Ret expression levels. These mice recapitulated the genetic and phenotypic fea

SUBMITTER: Uesaka T 

PROVIDER: S-EPMC2293334 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature