Phenotypes Associated with This Genotype

Genotype
MGI:3687001

• Allelic Composition: Npr1^tm1Kuhn/Npr1^tm1Kuhn; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

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

cardiovascular system

increased myocardial fiber size ( J:83298 )

• conditional mutants exhibit significantly increased ventricular cardiomyocyte diameters relative to homozygous Npr1^tm1Kuhn mice, in the absence of interstitial fibrosis

cardiac hypertrophy ( J:83298 )

• conditional mutants show a significant increase in the heart weight (HW) to body weight (BW) ratio relative to homozygous Npr1^tm1Kuhn mice

• under baseline conditions, cardiac ventricles from conditional mutants show elevated expression levels of cardiac hypertrophy genes ANP, alpha-skeletal-actin, and beta-MHC (~4.9-fold, ~1.7-fold, and ~2-fold, respectively); the beta-MHC/alpha-MHC ratio is increased by ~2.7-fold

• in response to pressure overload induced by transverse aortic constriction (TAC), conditional mutants show an enhanced cardiac hypertrophic response, with a significantly lower SBP and induced pressure gradient, a greater LVW/BW index but a similar mortality rate relative to homozygous Npr1^tm1Kuhn mice

cardiac interstitial fibrosis ( J:83298 )

• in response to pressure overload induced by TAC, conditional mutants show a slight increase in cardiac interstitial fibrosis relative to homozygous Npr1^tm1Kuhn mice (24% vs 8%, respectively)

abnormal cardiac muscle relaxation ( J:83298 )

• conditional mutants show normal heart rates and left ventricular contractility relative to homozygous Npr1^tm1Kuhn mice; in addition, chronotropic and inotropic responses to the beta-agonist dobutamine are preserved with no signs of cardiac dysfunction

• in contrast, baseline maximal relaxation rates and the lusitropic responses to low levels of beta-adrenergic stimulation are significantly reduced

decreased systemic arterial systolic blood pressure ( J:83298 )

• conditional mutants display slightly but significantly lower SBP relative to age- and sex-matched homozygous Npr1^tm1Kuhn mice, by ~7-10 mmHg

hypotension ( J:83298 )

• surprisingly, conditional mutants exhibit a mild but significant arterial hypotension by 7-10 mmHg

congestive heart failure ( J:83298 )

• in response to TAC-induced pressure load, conditional mutants display significant deterioration of cardiac function relative to TAC-operated homozygous Npr1^tm1Kuhn mice

• at 10-14 days after TAC, conditional mutants show decreased LV contractility and relaxation as well as increased LV end-diastolic pressure and greater ratios of lung weight (LW) and right ventricular weight (RVW) to BW, indicating congestive heart failure without clinical signs of RV failure

muscle

increased myocardial fiber size ( J:83298 )

• conditional mutants exhibit significantly increased ventricular cardiomyocyte diameters relative to homozygous Npr1^tm1Kuhn mice, in the absence of interstitial fibrosis

abnormal cardiac muscle relaxation ( J:83298 )

• conditional mutants show normal heart rates and left ventricular contractility relative to homozygous Npr1^tm1Kuhn mice; in addition, chronotropic and inotropic responses to the beta-agonist dobutamine are preserved with no signs of cardiac dysfunction

• in contrast, baseline maximal relaxation rates and the lusitropic responses to low levels of beta-adrenergic stimulation are significantly reduced

homeostasis/metabolism

increased circulating atrial natriuretic factor ( J:83298 )

• conditional mutants exhibit a >2-fold increase in plasma ANP levels relative to homozygous Npr1^tm1Kuhn mice

growth/size/body

cardiac hypertrophy ( J:83298 )

• conditional mutants show a significant increase in the heart weight (HW) to body weight (BW) ratio relative to homozygous Npr1^tm1Kuhn mice

• under baseline conditions, cardiac ventricles from conditional mutants show elevated expression levels of cardiac hypertrophy genes ANP, alpha-skeletal-actin, and beta-MHC (~4.9-fold, ~1.7-fold, and ~2-fold, respectively); the beta-MHC/alpha-MHC ratio is increased by ~2.7-fold

• in response to pressure overload induced by transverse aortic constriction (TAC), conditional mutants show an enhanced cardiac hypertrophic response, with a significantly lower SBP and induced pressure gradient, a greater LVW/BW index but a similar mortality rate relative to homozygous Npr1^tm1Kuhn mice

cellular

cardiac interstitial fibrosis ( J:83298 )

• in response to pressure overload induced by TAC, conditional mutants show a slight increase in cardiac interstitial fibrosis relative to homozygous Npr1^tm1Kuhn mice (24% vs 8%, respectively)