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.
Dr. Masashi Yanagisawa, Southwestern Medical School
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.
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 Name||targeted mutation 1, Masashi Yanagisawa|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||ET/A -|
|Gene Symbol and Name||Ednra, endothelin receptor type A|
|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.|
|Mutations Made By|| |
Dr. Masashi Yanagisawa, Southwestern Medical School
When maintained as a live colony, heterozygotes may be bred. Homozygotes are neonatal lethal, dying from mechanical asphyxia at birth.
When using the 129S-Ednratm1Ywa/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008865 in your Materials and Methods section.
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