Phenotypes associated with this allele

• Allele Symbol: Npr1^tm1Gar
• Allele Name: targeted mutation 1, David L Garbers
• Allele ID: MGI:2178776
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Npr1^tm1Gar/Npr1^tm1Gar	B6.129S7-Npr1^tm1Gar	MGI:3687148
hm2	Npr1^tm1Gar/Npr1^tm1Gar	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3640945
ht3	Npr1^tm1Gar/Npr1^+	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3640946

Genotype
MGI:3687148

hm1

• Allelic Composition: Npr1^tm1Gar/Npr1^tm1Gar
• Genetic Background: B6.129S7-Npr1^tm1Gar

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

decreased myocardial infarct size ( J:70496 )

• 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

impaired neutrophil chemotaxis ( J:70496 )

• 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

decreased myocardial infarct size ( J:70496 )

• 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

impaired neutrophil chemotaxis ( J:70496 )

• 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

impaired neutrophil chemotaxis ( J:70496 )

• 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

Genotype
MGI:3640945

hm2

• Allelic Composition: Npr1^tm1Gar/Npr1^tm1Gar
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

mortality/aging ( J:30007 )

N • 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

N • no histological abnormalities are detected in heart, vasculature or kidneys at less than 5 months of age

cardiovascular system

abnormal systemic arterial blood pressure ( J:42893 )

• 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

• 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

increased systemic arterial blood pressure ( J:30007 )

• 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

salt-resistant hypertension ( J:30007 )

• 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

• 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

increased systemic arterial diastolic blood pressure ( J:30007 )

• 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 ( J:30007 )

• 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

abnormal vasodilation ( J:42893 )

• 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)

homeostasis/metabolism

increased circulating atrial natriuretic factor ( J:42893 )

• 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

hydrops fetalis ( J:30007 )

• ~10% of homozygotes exhibit hydrops fetalis

muscle

abnormal vasodilation ( J:42893 )

• 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
MGI:3640946

ht3

• Allelic Composition: Npr1^tm1Gar/Npr1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system

increased systemic arterial blood pressure ( J:30007 )

• 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

salt-resistant hypertension ( J:30007 )

• 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

• 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

increased systemic arterial diastolic blood pressure ( J:30007 )

• 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 ( J:30007 )

• 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