Exon 3 is replaced by a neomycin resistance cassette in this knock-out mutant of the endothelin receptor type B (Ednrb) gene. Ednrb encodes a G protein-coupled receptor expressed in vascular endothelial cells where it is involved in vasoconstriction, vasodilation, bronchoconstriction and cell proliferation. In humans, mutations in this gene have been associated with Waardenburg syndrome type 4 (Waardenburg-Shah syndrome) which is characterized by deafness, neural crest defects, pigmentation changes, and Hirschsprung's disease. Hirschsprung's disease is primarily an intestinal disorder in which colon segments of variable length lack ganglion cells resulting in intestinal blockage and megacolon. Homozygous knock-out mice are initially viable but die within the first month. They show a disruption of neural crest lineage development, which is characterized by a lack of hair or skin pigmentation on 90% of their body. Death occurs by sepsis, likely from enterocolitis. Immunosuppression is evidenced by small spleens, bone marrow suppression, and thymic involution caused by the aganglionic megacolon. The phenotype is more severe (earlier onset enterocolitis and shorter life-span) on a congenic C57BL/6J strain than on the B6/129 hybrid background (Stock No. <a href="https://www.jax.org/strain/003295">003295</a>). They also do not breed as well and have smaller litters than the B6/129 line. This mutation is allelic with the piebald lethal spontaneous mutation.

This Ednrb knock-out exhibits an aganglionic megacolon, skin pigmentation deficiency and lymphoid depletion. They may be used as a model for human Hirschsprung's disease.

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