These G protein-coupled receptor 4 targeted mutation mice are phenotypically normal in adulthood. Neonates show a higher frequency of mortality, however. A fraction of knockout embryos and neonates have spontaneous hemorrhages, as well as dilated and tortuous subcutaneous blood vessels. The mice show impaired association of vascular smooth muscle cells with capillaries and small arteries and veins. Mesangial cells in kidney glomeruli are significantly reduced in homozygous targeted mice. In studies of vascular pH sensing, microvessel outgrowth from homozygous aortas is less inhibited by acidic extracellular pH. This strain may be useful in studies of vascular development and G protein receptor function.
Owen Witte, University of California, Los Angeles
These G protein-coupled receptor 4 targeted mutation mice are phenotypically normal in adulthood. Neonates show a higher frequency of mortality, however. Homozygous crosses produce litter sizes that are approximately 30% smaller than wild-type intercrosses on a C57BL/6 genetic background (backcross generations N3 and N5). A fraction of knockout embryos and neonates have spontaneous hemorrhages, as well as dilated and tortuous subcutaneous blood vessels. The mice show impaired association of vascular smooth muscle cells with capillaries and small arteries and veins. Mesangial cells in kidney glomeruli are significantly reduced in homozygous targeted mice. There is impaired contact between mesangial cells and renal glomerular capillaries. Some neonates exhibit respiratory distress with airway lining cell metaplasia. In studies of vascular pH sensing, microvessel outgrowth from homozygous aortas is less inhibited by acidic extracellular pH. Although an IRES-GFP insertion was incorporated in this strain, it can not be reliably observed through microscopy. This strain may be useful in studies of vascular development and G protein receptor function.
The open reading frame of the gene was replaced with IRES-GFP and a PGK-neomycin resistance cassette. The targeting vector was introduced to 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6J blastocysts, and then backcrossed to the same for more than 6 generations.
|Allele Name||targeted mutation 1, Owen N Witte|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Gpr4, G protein-coupled receptor 4|
|Strain of Origin||129X1/SvJ|
|Molecular Note||The coding region was replaced by the IRES-GFP and PGK-neo cassette. Absence of transcript was confirmed by RT-PCR.|
|Mutations Made By|| |
Owen Witte, University of California, Los Angeles
When maintained as a live colony, heterozygotes or homozygotes may be bred. Homozygous crosses produce litters that are notably smaller than wildtype crosses due to perinatal lethality.
When using the B6.129X1-Gpr4tm1Witt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008580 in your Materials and Methods section.
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