Phenotypes for Npr1 MGI:3665579 MGI Mouse

mortality/aging ( J:101857 )

N	• Background Sensitivity: sudden death occuring in F2 generation males of a mixed genetic background is no longer present in homozygotes after 6 or 7 backcrosses to C57BL/6, possibly due to genetic drifts and loss of modifying loci

enlarged heart ( J:78579 )

• adult homozygotes have significantly larger hearts than wild-type mice, as shown by increased HW/BW ratios

cardiac hypertrophy ( J:78579 , J:101857 )

• adult homozygotes exhibit cardiac hypertrophy versus wild-type mice at baseline (J:78579)

• in response to volume overlaod, homozygotes with aortocaval fistula display a change in LV geometry from concentric cardiac hypertrophy to borderline of concentric and eccentric hypertrophy (J:101857)

• in contrast, wild-type with aortocaval fistula exhibit a change in LV geometry from a normal pattern to eccentric hypertrophy (J:101857)

hypertension ( J:78579 )

• adult homozygotes (4-12 months) have significantly higher blood pressure levels than wild-type control mice (126 3 mmHg vs 108 2 mmHg, respectively)

• however, no significant difference in blood pressures between male and female homozygotes is observed

congestive heart failure ( J:101857 )

• in response to volume overlaod, homozygotes with aortocaval fistula exhibit increased susceptibility to heart failure, as shown by higher LV end-diastolic pressure, LV and RV weights, atrial weights, lung weight, and LV dimension, as well as lower fractional shortening and urinary sodium and cyclic guanosine monophosphate (cGMP) excretion than wild-type mice with aortocaval fistula

• ventricular mRNA expression of natriuretic peptides and beta-myosin heavy chain increases significantly only in mutant mice with aortocaval fistula

• plasma ANP, renin, and aldosterone, but not cGMP, exhibit greater responses to aortocaval fistula in homozygous mutant mice

• both sham-operated and aortocaval fistula heterozygous mice almost consistently display a phenotype intermediate between those of homozygous and wild-type mice

increased circulating atrial natriuretic factor ( J:78579 )

• adult male (but not female) homozygotes display significantly higher circulating ANP levels relative to sex-matched wild-type counterparts

• in contrast to wild-type mice, male homozygotes have significantly greater levels of plasma ANP than female homozygotes

• however, a greater increase in ventricular ANP and BNP gene expression and ANP immunoreactivity is noted in female vs male homozygotes; increased expression is highly correlated to the degree of cardiac hypertrophy and is localized to the LV inner free wall and to areas of ventricular fibrosis