cardiovascular system phenotype

• 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
  (MGI Ref ID J:30007)

• 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
  (MGI Ref ID J:30007)

• 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
  (MGI Ref ID J:30007)

• salt-resistant hypertension
  • 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
  (MGI Ref ID J:30007)
  • 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
  (MGI Ref ID J:30007)

homeostasis/metabolism phenotype

• increased circulating atrial natriuretic factor
  • in contrast, basal concentrations of circulating CNP are below the detectable limit in both wild-type and mutant mice
  (MGI Ref ID J:42893)
  • homozygous mutant mice exhibit increased basal concentrations of ANP relative to wild-type mice (~279 ¿ 109 pM vs ~159 ¿ 111 pM, respectively)
  (MGI Ref ID J:42893)

• hydrops fetalis
  • ~10% of homozygotes exhibit hydrops fetalis
  (MGI Ref ID J:30007)

mammalian phenotype

• mortality/aging
  • Normal - no histological abnormalities are detected in heart, vasculature or kidneys at less than 5 months of age
  (MGI Ref ID J:30007)
  • 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
  (MGI Ref ID J:30007)

muscle phenotype

• abnormal vasodilation
  • 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)
  (MGI Ref ID 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
  (MGI Ref ID J:42893)

cardiovascular system phenotype

• 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
  (MGI Ref ID J:30007)

• 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
  (MGI Ref ID 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
  (MGI Ref ID J:30007)

• 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
  (MGI Ref ID J:30007)

• abnormal systemic arterial blood pressure
  • 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
  (MGI Ref ID J:42893)
  • 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
  (MGI Ref ID J:42893)

• 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
  (MGI Ref ID J:30007)

• abnormal vasodilation
  • 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)
  (MGI Ref ID 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
  (MGI Ref ID J:42893)

cardiovascular system phenotype

• decreased myocardial infarction size
  • reduced infarct size is associated with concomitant reductions in PMN infiltration, coronary endothelial cell expression of P-selectin, and activation of NF-kappaB
  (MGI Ref ID J:70496)
  • at 2 days after myocardial ischemia/reperfusion, homozygotes exhibit a 20% reduction in myocardial infarct size relative to wild-type mice
  (MGI Ref ID J:70496)

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
  (MGI Ref ID J:70496)
  • reduced PMN emigration is corroborated by reduced cardiac MPO activity in infarct areas of mutant mice
  (MGI Ref ID J:70496)

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
  (MGI Ref ID J:70496)
  • reduced PMN emigration is corroborated by reduced cardiac MPO activity in infarct areas of mutant mice
  (MGI Ref ID J:70496)

homeostasis/metabolism phenotype

• decreased myocardial infarction size
  • reduced infarct size is associated with concomitant reductions in PMN infiltration, coronary endothelial cell expression of P-selectin, and activation of NF-kappaB
  (MGI Ref ID J:70496)
  • at 2 days after myocardial ischemia/reperfusion, homozygotes exhibit a 20% reduction in myocardial infarct size relative to wild-type mice
  (MGI Ref ID J:70496)

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
  (MGI Ref ID J:70496)
  • reduced PMN emigration is corroborated by reduced cardiac MPO activity in infarct areas of mutant mice
  (MGI Ref ID J:70496)