Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice

Kiminori Hosoda, Robert E Hammer, James A Richardson, Amy Greenstein Baynash, Jason C. Cheung, Adel Giaid, Masashi Yanagisawa

Research output: Contribution to journalArticle

839 Scopus citations

Abstract

Endothelins act on two subtypes of G protein-coupled receptors, termed endothelin-A and endothelin-B receptors. We report a targeted disruption of the mouse endothelin-B receptor (EDNRB) gene that results in aganglionic megacolon associated with coat color spotting, resembling a hereditary syndrome of mice, humans, and other mammalian species. Piebald-lethal (sl) mice exhibit a recessive phenotype identical to that of the EDNRB knockout mice. In crossbreeding studies, the two mutations show no complementation. Southern blotting revealed a deletion encompassing the entire EDNRB gene in the sl chromosome. A milder allele, piebald (s), which produces coat color spotting only, expresses low levels of structurally intact EDNRB mRNA and protein. These findings indicate an essential role for EDNRB in the development of two neural crest-derived cell lineages, myenteric ganglion neurons and epidermal melanocytes. We postulate that defects in the human EDNRB gene cause a hereditary form of Hirschsprung's disease that has recently been mapped to human chromosome 13, in which EDNRB is located.

Original languageEnglish (US)
Pages (from-to)1267-1276
Number of pages10
JournalCell
Volume79
Issue number7
DOIs
StatePublished - Dec 30 1994

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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