B6;129-Ednrb^tm1Ywa/J

Stock number: 003295
Research areas: Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

This strain may be used as a model for human Hirschsprung's disease.

Detailed description

In this strain, a neo cassette replaces exon 3 of the endothelin receptor type B (Ednrb) gene, abolishing gene function. Ednrb encodes a G protein-coupled receptor expressed in vascular endothelial cells where it is involved in vasoconstriction, vasodilation, bronchoconstriction and cell proliferation. Mutations have been associated with Waardenburg syndrome type 4 (Waardenburg-Shah syndrome) characterized by deafness, neural crest defects, pigmentation changes, and Hirschsprung's disease. Hirschsprung's disease is an intestinal disorder that causes intestinal blockage. Homozygotes are viable but usually die within the first month of life. 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. They die due to peritonitis from distention caused by an aganglionic megacolon. The phenotype is less severe on this B6/129 hybrid background than on the congenic C57BL/6J background (Stock No. 021933) in that these mice tend to have later onset enterocolitis and have a longer life-span. This mutation is allelic with the piebald lethal spontaneous mutation.

Development

A targeting vector was designed to replace exon 3 of the endothelin receptor type B (Ednrb) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-derived JH-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Ednrb^tm1Ywa
Name: targeted mutation 1, Masashi Yanagisawa
MGI accession ID: MGI:1857161
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ednrb
Marker name: endothelin receptor type B
Chromosome: 14
Strain of origin: 129S7/SvEvBrd
Molecular note: A neomycin resistance cassette replaced a 4.2kb segment of the gene, which contained exon 3. Exon 3 encodes the fourth transmembrane helix of the protein. Functional analysis showed that the allele is null.