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
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Gpr4 | G protein-coupled receptor 4 |
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 |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Gpr4- |
Gene Symbol and Name | Gpr4, G protein-coupled receptor 4 |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 7 |
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.
Facility Barrier Level Descriptions
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Heterozygous for Gpr4<tm1Witt> |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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