Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Pera et al found associated of NPR3 polymorphism with POF.

Species: mouse
Mutation name: Npr 1 gene
type: null mutation
fertility: fertile
Comment: To study the role of NPRA in the regulation of blood pressure and in the cardiovascular response to sustained hypertension, Oliver et al. Oliver et al. (1997) made mice completely lacking this receptor. These mice showed elevated blood pressures and heart exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease. From echocardiographic evaluation of the mice, it became evident that these mice were in a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation were evident but with no reduction in ventricular performance. Nonetheless, all male mice (before 6 months of age) and 1 of the 16 female mice died suddenly and exhibited morphologic evidence indicative of congestive heart failure in some and aortic dissection in others.

Species: mouse
Mutation name: guanylyl cyclase-A (GC-A) natriuretic peptide receptor gene
type: null mutation
fertility: fertile
Comment: Lopez et al. Lopez et al. (1997) disrupted the guanylyl cyclase-A (GC-A) natriuretic peptide receptor in mice in order to determine which of the natural peptides with natriuretic peptide-like structures regulate blood pressure through the GC-A receptor. Atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP) half-maximally relaxed precontracted aortic rings in wild-type mice, but failed to relax such aortas in GC-A null mice. C-type natriuretic peptide (CNP), in contrast, caused half-maximal relaxation at concentrations in aortas from either wild-type or null mice, respectively, suggesting that this peptide acted through a receptor other than GC-A. Since the in vitro results with aortic smooth muscle do not necessarily reflect the physiology of the smaller blood vessels important in blood pressure regulation, the blood pressures of conscious mice infused with the various peptides were determined. ANP caused decreases in blood pressure and plasma concentrations of 0.8 nM. In the null mice, in contrast, ANP failed to lower blood. Much higher infusion rates for, which yielded final plasma concentrations of 18.3 nM, were required to lower blood pressure in wild-type mice, but the effects of CNP were not altered in GC-A null mice. Thus, two natriuretic peptides (ANP, BNP) act through GC-A whereas another (CNP) acts through another receptor to regulate blood pressure.

Species: mouse
Mutation name: guanylyl cyclase-A (GC-A) natriuretic peptide receptor gene
type: targeted overexpression
fertility: fertile
Comment: To determine whether Npr1 gene function affects the testosterone level, Pandey et al. Pandey et al. (1999) measured serum testosterone in male hypertensive mice lacking a functional Npr1 gene, wild-type animals with two copies, and the gene-duplicated littermates expressing four copies of the gene. In the Npr1 gene-knockout (zero-copy) mice, the serum testosterone level was 62% lower than that in the two-copy control mice (80+/-10 ts. 120+/-14 ng/ml, respectively; P < 0.005). Serum testosterone in the four-copy mice was 144% (P < 0.005) of that in the two-copy wild-type control mice. To investigate the role of NPRA in testicular steroidogenesis, we analyzed atrial natriuretic peptide (ANP)-dependent guanylyl cyclase activation, accumulation of intracellular cGMP, and testosterone production in purified primary Leydig cells from animals with zero, two, or four copies of the Npr1 gene. ANP-dependent guanylyl cyclase activation and production of cGMP in Leydig cells increased progressively with the number of Npr1 gene copies. Their results establish the existence of an alternate mechanism for testicular steroidogenesis that is stimulated by NPRA-dependent cGMP signaling, in addition to that mediated by gonadotropins, via a cAMP pathway. These findings demonstrate the role of Npr1 gene function in the maintenance of serum testosterone levels and testicular steroidogenesis and provide a genetic link between hypertension associated with decreased NPRA and low testosterone levels.