Baynash AG, Hosoda K, Giaid A, Richardson JA, Emoto N, Hammer RE, Yanagisawa M:
Interaction of endothelin-3 with endothelin-B receptor is essential
for development of epidermal melanocytes and enteric neurons.
Cell 1994 Dec 30;79(7):1277-85
ABSTRACT
Defects in the gene encoding the endothelin-B receptor produce
aganglionic megacolon and pigmentary disorders in mice and humans.
We report that a targeted disruption of the mouse endothelin-3
ligand (EDN3) gene produces a similar recessive phenotype of
megacolon and coat color spotting. A natural recessive mutation that
results in the same developmental defects in mice, lethal spotting
(ls), failed to complement the targeted EDN3 allele. The ls mice
carry a point mutation of the EDN3 gene, which replaces the Arg
residue at the C-terminus of the inactive intermediate big EDN3 with
a Trp residue. This mutation prevents the proteolytic activation of
big EDN3 by ECE-1. These findings indicate that interaction of EDN3
with the endothelin-B receptor is essential in the development of
neural crest-derived cell lineages. We postulate that defects in the
human EDN3 gene may cause Hirschsprung's disease.
