Overview

Also Known As:GC-A KO

These Npr1 knock-out mice exhibit elevated systolic, diastolic and mean blood pressure.

Donating Investigator

David L. Garbers, U.T. Southwestern Medical Center

Genetic overview

Genetic Background	Generation

Npr1^tm1Gar

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Npr1	natriuretic peptide receptor 1

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Research Applications

Cardiovascular Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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.

Control Suggestions

002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Lopez MJ; Wong SK; Kishimoto I; Dubois S; Mach V; Friesen J; Garbers DL; Beuve A. 1995. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature 378(6552):65-8PubMed: 7477288 MGI: J:30007

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Genetics

Npr1^tm1Gar

Allele Symbol: Npr1^tm1Gar

Allele Name	targeted mutation 1, David L Garbers
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Npr1^tm1Gar related

Cardiovascular Research
- Heart Abnormalities
- Hypertension

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Npr1^tm1Gar/Npr1^tm1Gar
involves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system phenotype

abnormal systemic arterial blood pressure
- CNP evoked a significant reduction in BP at much higher infusion rates (50 ¿g/kg/min), resulting in a plasma concentration of 18.3 nM, with no significant differences between wild-type and mutant mice
- in wild-type mice, ANP evoked a significant reduction in BP at 500 ng/kg/min, a rate which resulted in a plasma concentration of 0.8 nM; in contrast, ANP failed to lower BP in mutant mice even at infusion rates of 50 ¿g/kg/min

abnormal vasodilation
- atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP) half-maximally relaxed KCl-precontracted aortic rings in wild-type mice at ~24 nM, but failed to relax aortas in mutant mice, even at micromolar concentrations
- in contrast, C-type natriuretic peptide (CNP) caused half-maximal relaxation at 335 and 146 nM in aortas from either wild-type or null mice, respectively (no significant difference)

increased systemic arterial blood pressure
- on a standard rodent chow (0.7% NaCl), homozygotes exhibit a 19.7 mm Hg increase in mean blood pressure relative to wild-type mice; no significant changes in heart rates are observed

increased systemic arterial diastolic blood pressure
- on a standard rodent chow (0.7% NaCl), homozygotes exhibit a 15.3 mm Hg increase in diastolic blood pressure relative to wild-type mice

increased systemic arterial systolic blood pressure
- on a standard rodent chow (0.7% NaCl), homozygotes exhibit a 27.4 mm Hg increase in systolic blood pressure relative to wild-type mice

salt-resistant hypertension
- a high (8% NaCl) salt diet fails to change hematocrit or body weight, suggesting the possibility of increased natriuresis; no differences in aldosterone and atrial natriuretic peptide concentrations are observed
- homozygotes display salt-resistant hypertension: on a low (0.008% NaCl), normal (0.7% NaCl) and high (8% NaCl) salt diet, their blood pressures and heart rates remain unchanged

homeostasis/metabolism phenotype

hydrops fetalis
- ~10% of homozygotes exhibit hydrops fetalis

increased circulating atrial natriuretic factor
- homozygous mutant mice exhibit increased basal concentrations of ANP relative to wild-type mice (~279 ¿ 109 pM vs ~159 ¿ 111 pM, respectively)
- in contrast, basal concentrations of circulating CNP are below the detectable limit in both wild-type and mutant mice

mammalian phenotype

mortality/aging
- Normal - at 3 weeks, homozygotes are slightly (but significantly) underrepresented, at least partly due to the presence of hydrops fetalis in 10% of mutant embryos; however, stage of lethality is not speficied
- Normal - no histological abnormalities are detected in heart, vasculature or kidneys at less than 5 months of age

muscle phenotype

abnormal vasodilation
- atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP) half-maximally relaxed KCl-precontracted aortic rings in wild-type mice at ~24 nM, but failed to relax aortas in mutant mice, even at micromolar concentrations
- in contrast, C-type natriuretic peptide (CNP) caused half-maximal relaxation at 335 and 146 nM in aortas from either wild-type or null mice, respectively (no significant difference)

Genotype: Npr1^tm1Gar/Npr1⁺
involves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system phenotype

increased systemic arterial blood pressure
- on a standard rodent chow (0.7% NaCl), heterozygotes exhibit a 7.7 mm Hg increase in mean blood pressure relative to wild-type mice; no significant changes in heart rates are observed

increased systemic arterial diastolic blood pressure
- on a standard rodent chow (0.7% NaCl), heterozygotes exhibit a 5.9 mm Hg increase in diastolic blood pressure relative to wild-type mice

increased systemic arterial systolic blood pressure
- on a standard rodent chow (0.7% NaCl), heterozygotes exhibit a 10.5 mm Hg increase in systolic blood pressure relative to wild-type mice

salt-resistant hypertension
- a high (8% NaCl) salt diet fails to change hematocrit or body weight, suggesting the possibility of increased natriuresis; no differences in aldosterone and atrial natriuretic peptide concentrations are observed
- heterozygotes display salt-resistant hypertension: on a low (0.008% NaCl), normal (0.7% NaCl) and high (8% NaCl) salt diet, their blood pressures and heart rates remain unchanged

Genotype: Npr1^tm1Gar/Npr1^tm1Gar
B6.129S7-Npr1

cardiovascular system phenotype

decreased myocardial infarction size
- at 2 days after myocardial ischemia/reperfusion, homozygotes exhibit a 20% reduction in myocardial infarct size relative to wild-type mice
- reduced infarct size is associated with concomitant reductions in PMN infiltration, coronary endothelial cell expression of P-selectin, and activation of NF-kappaB

cellular phenotype

impaired neutrophil chemotaxis
- in response to myocardial ischemia/reperfusion, homozygotes exhibit a significant reduction in the number of PMNs infiltrating the myocardium relative to wild-type mice
- reduced PMN emigration is corroborated by reduced cardiac MPO activity in infarct areas of mutant mice

hematopoietic system phenotype

impaired neutrophil chemotaxis
- in response to myocardial ischemia/reperfusion, homozygotes exhibit a significant reduction in the number of PMNs infiltrating the myocardium relative to wild-type mice
- reduced PMN emigration is corroborated by reduced cardiac MPO activity in infarct areas of mutant mice

homeostasis/metabolism phenotype

decreased myocardial infarction size
- at 2 days after myocardial ischemia/reperfusion, homozygotes exhibit a 20% reduction in myocardial infarct size relative to wild-type mice
- reduced infarct size is associated with concomitant reductions in PMN infiltration, coronary endothelial cell expression of P-selectin, and activation of NF-kappaB

immune system phenotype

impaired neutrophil chemotaxis
- in response to myocardial ischemia/reperfusion, homozygotes exhibit a significant reduction in the number of PMNs infiltrating the myocardium relative to wild-type mice
- reduced PMN emigration is corroborated by reduced cardiac MPO activity in infarct areas of mutant mice

References

Lopez MJ; Wong SK; Kishimoto I; Dubois S; Mach V; Friesen J; Garbers DL; Beuve A. 1995. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature 378(6552):65-8PubMed: 7477288 MGI: J:30007

Additional - Npr1^tm1Gar related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Npr1
- Genotyping resources and troubleshooting
Breeding Considerations

This strain originated on a 129S7 background and is maintained on the 129S6/SvEvTac background as a heterozygote.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Npr1<tm1Gar>

Related Products and Services

Frozen Mouse Embryo	129-Npr1<tm1Gar>/J Frozen Embryos	$2595.00
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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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Also Known As:GC-A KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Npr1tm1Gar

Allele Symbol: Npr1tm1Gar

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Npr1tm1Gar related

Mammalian Phenotype Terms by Genotype

Genotype: Npr1tm1Gar/Npr1tm1Garinvolves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system phenotype

homeostasis/metabolism phenotype

mammalian phenotype

muscle phenotype

Genotype: Npr1tm1Gar/Npr1+involves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system phenotype

Genotype: Npr1tm1Gar/Npr1tm1GarB6.129S7-Npr1

cardiovascular system phenotype

cellular phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional - Npr1tm1Gar related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Npr1^tm1Gar

Allele Symbol: Npr1^tm1Gar

Genotype: Npr1^tm1Gar related

Genotype: Npr1^tm1Gar/Npr1^tm1Gar
involves: 129S7/SvEvBrd * C57BL/6J

Genotype: Npr1^tm1Gar/Npr1⁺
involves: 129S7/SvEvBrd * C57BL/6J

Genotype: Npr1^tm1Gar/Npr1^tm1Gar
B6.129S7-Npr1

Additional - Npr1^tm1Gar related