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. 2013 Jun 17;123(7):3084–3098. doi: 10.1172/JCI64401

Figure 3. Double conditional knockout of Sirt1 and Pkd1 delayed renal cyst formation.

Figure 3

(A–D) Histologic examination of P7 kidneys from (A) Pkd1+/+:Sirt1flox/flox:Ksp-Cre, (B) Pkd1flox/flox:Sirt1+/+:Ksp-Cre, (C) Pkd1flox/flox:Sirt1flox/+:Ksp-Cre, and (D) Pkd1flox/flox:Sirt1flox/flox:Ksp-Cre neonates. (E) Percent cystic area relative to total kidney section area was significantly decreased in P7 kidneys from Pkd1flox/flox:Sirt1flox/flox:Ksp-Cre (Sirt1flox/flox) versus Pkd1flox/flox:Sirt1+/+:Ksp-Cre (Sirt1+/+) neonates. Data reflect all sections quantified for each condition (n = 10 per group). (F) KW/BW ratios were dramatically reduced in P7 Pkd1flox/flox:Sirt1flox/flox:Ksp-Cre versus Pkd1flox/flox:Sirt1+/+:Ksp-Cre neonates. (G) BUN levels of P7 Pkd1flox/flox:Sirt1+/+:Ksp-Cre, Pkd1flox/flox:Sirt1flox/+:Ksp-Cre, and Pkd1flox/flox:Sirt1flox/flox:Ksp-Cre neonates. (H) Cell proliferation (arrows) was decreased in P7 Pkd1flox/flox:Sirt1flox/flox:Ksp-Cre versus Pkd1flox/flox:Sirt1+/+:Ksp-Cre neonate kidneys, as detected with PCNA staining. The percentage of PCNA-positive nuclei in cystic lining epithelial cells was calculated from an average of 1,000 nuclei per mouse kidney section; only strongly stained nuclei were considered PCNA-positive. (I) Pkd1flox/flox:Sirt1flox/flox:Ksp-Cre mice lived to 21.9 ± 3.6 days, whereas Pkd1flox/flox:Sirt1+/+:Ksp-Cre mice died of polycystic kidney disease at 14.1 ± 0.9 days. Scale bars: 2 mm (A–D); 30 μm (H). *P < 0.05; **P < 0.01.