Fig 2: A) Body weight and kidney weight as percent of body weight (%KW/BW) in wild-type mice and in Pde1aDel15 and Pde1aInsA homozygous mice or data from both combined. B) Axial and coronal MR images of Pde1a mutant mice at 6 and 12 months of age showing small renal cysts (arrows; this panel is also shown as a larger figure in Fig B in S1 File). C) Kidney sections from Pde1aDel15 and Pde1aInsA homozygous mice showing multiple small cysts staining positively for Tamm-Horsfall protein and epithelial membrane antigen, less consistently for aquaporin-2, and not staining for lysozyme. D) Reduced urine osmolality after 24 hours of dehydration, faster excretion of an acute water load, and E) reduced expression of glycosylated (upper band) and unglycosylated (lower band) pSer269-AQP2 in Pde1aDel15 and Pde1aInsA homozygotes compared to wild-type mice. One-way ANOVA with post-hoc Tukey test was used for the statistical analysis.

Fig 3: A) Total PDE, PDE1, PDE3 and PDE4 activities in kidney and heart lysates from wild-type mice and from Pde1aDel15 and Pde1aInsA homozygous mice or results of both combined. B) Western blots of kidney and heart lysates from six wild-type mice detected with PDE1A, PDE1B and PDE1C antibodies; total protein stain with Coomassie Blue is used as a loading control. C) Cyclic AMP and cGMP levels in kidney and heart lysates from wild-type mice and from Pde1aDel15 and Pde1aInsA homozygous mice or results of both combined. D) Western blot of kidney, heart, aorta, liver, spleen and brain lysates from wild-type and Pde1aInsA homozygous mice detected with a PDE1A antibody; a weak cardiac band can be seen in wild-type with longer exposure (data not shown). One-way ANOVA with post-hoc Tukey test was used for the statistical analysis.

Fig 4: PCNA immunostaining of kidney sections (x 200) in wild-type mice (n = 4) and in Pde1aDel15 (n = 5) or Pde1aInsA (n = 3) homozygous mice, and both combined (n = 8).Proliferative indices were significantly higher in the Pde1a mutants compared to the wild type mice. One-way ANOVA with post-hoc Tukey test was used for the statistical analysis.

Fig 5: A) Aortic blood pressures were lower in Pde1aDel15 and Pde1aInsA homozygous mice compared to wild-type mice. B) Echocardiographic studies showing increased LV ejection fractions in Pde1aDel15 and Pde1aInsA homozygous mice compared to wild-types; RV: Right ventricle; LV: Left ventricle; IVS: Interventricular septum; PW: Posterior wall C) Measurements of LV mass index using MRI show no significant difference between wild-type and Pde1a mutant mice. One-way ANOVA with post-hoc Tukey test was used for the statistical analysis.