These Npr1 knock-out mice exhibit elevated systolic, diastolic and mean blood pressure.
David L. Garbers, U.T. Southwestern Medical Center
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Npr1 | natriuretic peptide receptor 1 |
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) was detected. Homozygous mutant mice have elevated systolic, diastolic and mean blood pressure when compared to wildtype. Heterozygous mutant mice display systolic, diastolic and mean blood pressure that are slightly elevated above wildtype levels. Blood pressure in mutant mice remains elevated independent of salt content in diet. Infusion treatment of atrial natriuretic peptide in mutant mice does not result in the increased urine output or sodium excretion response seen in wildtype mice. Plasma volume expansion to release natriuretic/diuretic factors from the heart fails to induce increased urine output, sodium excretion and cyclic GMP excretion in the mutant. The same plasma volume expansion in wildtype mice results in a 12-fold increase in urine output, a 6-fold increase in sodium excretion and a 4-fold increase in cyclic GMP excretion in the urine. Mutant mice excrete only 30% of the normal level of urinary cyclic GMP. The Donating Investigator reports this mutant strain also exhibits cardiac hypertrophy and cardiac fibrosis. The phenotype of this mutant strain, salt insensitive hypertension, resembles that of half of all human patients with essential hypertension. This mutant mouse strain represents a model that may be useful in studies related to essential hypertension.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 4 of the targeted gene. The construct was electroporated into 129S7/SvEvBrd-Hprt+ derived AB-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
Allele Name | targeted mutation 1, David L Garbers |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | GC-A KO; GC-A- |
Gene Symbol and Name | Npr1, natriuretic peptide receptor 1 |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 3 |
Molecular Note | Insertion of a neomycin resistance cassette into exon 4, which encodes part of the extra-cellular putative ligand-binding domain, disrupted the gene. Stable, wild-type size transcript was not detected in liver or kidney from homozygous mutant mice. |
Mutations Made By | David Garbers, U.T. Southwestern Medical Center |
This strain originated on a 129S7 background and is maintained on the 129S6/SvEvTac background as a heterozygote.
When using the GC-A KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004374 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Npr1<tm1Gar> |
Frozen Mouse Embryo | 129-Npr1<tm1Gar>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | 129-Npr1<tm1Gar>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | 129-Npr1<tm1Gar>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | 129-Npr1<tm1Gar>/J Frozen Embryos | $3373.50 |
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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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