129S-Ednra^tm1Ywa/J

Stock number: 008865
Research areas: Developmental Biology Research

Description

Homozygous Ednra (endothelin receptor type A) targeted mutant embryos are born with numerous defects in craniofacial structures. Defects also exist in the heart, including double outlet right ventricle, transposition of the great arteries, interruption of the aorta and persistent truncus arteriosus.

Detailed description

Homozygous endothelin receptor type A targeted mutant embryos are born with numerous defects in craniofacial structures. The mandible appears to have undergone a homeotic transformation into a maxilla. Other maxillary structures are duplicated in the lower jaw, including the palatine, jugal and pterygoid bones. The malleus and incus of the middle ear are dysmorphic and Meckel's cartilage is absent. The hyoid bone of the throat is moved rostrally and fused with the pterygoid bones, resulting in collapse of the trachea and subsequent asphyxia. Defects also exist in the heart, including double outlet right ventricle, transposition of the great arteries, interruption of the aorta and persistent truncus arteriosus. While all mutant mice have cardiac defects, the specific type of defect differs between embryos. Expression of the targeted gene (total embryo RNA) is still observed in homozygous mutant embryos, though there is a shift in size, suggestive of a partial mRNA. Ligand binding assays confirm that no functional receptor is present in the mutant embryos, however.

Development

Exons 5 and 6 of the targeted gene, corresponding to the sixth and seventh transmembrane domains, were replaced with a neomycin resistance cassette driven by the RNA polymerase II promoter. The targeting construct was electroporated into 129S7/SvEvBrd-derived JH1 embryonic stem (ES) cells. Correctly targeted ES cell clones were injected into C57BL/6 blastocysts. Mice were bred to 129S6/SvEvTac mice.

Allele

Symbol: Ednra^tm1Ywa
Name: targeted mutation 1, Masashi Yanagisawa
MGI accession ID: MGI:1857473
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ednra
Marker name: endothelin receptor type A
Chromosome: 8
Strain of origin: 129S7/SvEvBrd
Molecular note: A neomycin selection cassette replaced a genomic fragment containing exons 5 and 6, which encode the sixth and seventh transmembrane domains of the protein. Radioligand binding assays on samples derived from skin of homozygous embryos demonstrated that no functional protein was produced from this allele.