Endothelin receptor B (Ednrb) plays a critical role in the development of 
melanocytes and neurons and glia of the enteric nervous system. These distinct 
neural crest-derived cell types express Ednrb and share the property of 
intercalating into tissues, such as the intestine whose muscle precursor cells 
also express Ednrb. Such widespread Ednrb expression has been a significant 
obstacle in establishing precise roles for Ednrb in development. We describe 
here the production of an Ednrb allele floxed at exon 3 and its use in excising 
the receptor from mouse neural crest cells by use of Cre-recombinase driven by 
the Wnt1 promoter. Mice born with neural crest-specific excision of Ednrb 
possess aganglionic colon, lack trunk pigmentation, and die within 5 weeks due 
to megacolon. Ednrb receptor expression in these animals is absent only in the 
neural crest but present in surrounding smooth muscle cells. The absence of 
Ednrb from crest cells also results in a compensatory upregulation of Ednrb 
expression in other cells within the gut. We conclude that Ednrb loss only in 
neural crest cells is sufficient to produce the Hirschsprungs disease phenotype 
observed with genomic Ednrb mutations.