| http://purl.uniprot.org/citations/33958373 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33958373 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations of the gene encoding the RET tyrosine kinase causes Hirschsprung's disease (HSCR) and medullary thyroid carcinoma (MTC). Current consensus holds that HSCR and MTC are induced by inactivating and activating RET mutations, respectively. However, it remains unknown whether activating mutations in the RET gene have adverse effects on ENS development in vivo We addressed this issue by examining mice engineered to express RET51(C618F), an activating mutation identified in MTC patients. Although Ret51(C618F)/51(C618F) mice displayed hyperganglionosis of the ENS, Ret51(C618F)/- mice exhibited severe intestinal aganglionosis because of premature neuronal differentiation. Reduced levels of glial cell-derived neurotrophic factor (GDNF), a RET-activating neurotrophic factor, ameliorated the ENS phenotype of Ret51(C618F)/- mice, demonstrating that GDNF-mediated activation of RET51(C618F) is responsible for severe aganglionic phenotype. The RET51(C618F) allele showed genetic interaction with Ednrb gene, one of modifier genes for HSCR. These data reveal that proliferation and differentiation of ENS precursors are exquisitely controlled by both the activation levels and total dose of RET. Increased RET activity coupled with a decreased gene dosage can cause intestinal aganglionosis, a finding that provides novel insight into HSCR pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.org/dc/terms/identifier | "doi:10.1523/eneuro.0534-20.2021"xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/author | "Ito K."xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/author | "Okamoto M."xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/author | "Enomoto H."xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/author | "Uesaka T."xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/name | "eNeuro"xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/pages | "ENEURO.0534-20.2021"xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/title | "Increased RET Activity Coupled with a Reduction in the RET Gene Dosage Causes Intestinal Aganglionosis in Mice."xsd:string |
| http://purl.uniprot.org/citations/33958373 | http://purl.uniprot.org/core/volume | "8"xsd:string |
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