The protein encoded by EDNRB is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. Studies suggest that the multigenic disorder, Hirschsprung disease type 2, is due to mutations in the endothelin receptor type B gene. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

The CDS that encodes human EDNRB signal peptide and extracellular domain, transmembrane and cytoplasmic domain, followed by mouse 3’UTR-STOP is inserted right after mouse Ednrb ATG to replace the exon 1 of mouse Ednrb gene. The EDNRB protein expression will be driven by endogenous mouse Ednrb promoter, while mouse Ednrb gene transcription and translation will be disrupted.

EDNRB protein was detected in cortex, liver, spleen, lung and kidney from wild-type C57BL/6 mice and homozygous B-hEDNRB mice as the antibody is cross-recognize with human and mouse.

Mouse Ednrb mRNA was detectable only in wild-type C57BL/6 mice. Human EDNRB mRNA was detectable only in homozygous B-hEDNRB mice, but not in wild-type C57BL/6 mice.

All homozygous B-hEDNRB mice have a coat color phenotype, with white fur on the abdomen.

Western blot analysis of EDNRB protein expression in homozygous B-hEDNRB mice. Various tissue lysates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hEDNRB mice (H/H), and then analyzed by western blot with anti-EDNRB antibody (abcam, ab129102). 30 μg total proteins were loaded for western blotting analysis. EDNRB was detected in cortex, liver, spleen, lung and kidney from wild-type C57BL/6 mice and homozygous B-hEDNRB mice as the antibody is cross-recognize with human and mouse.