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. 2022 Mar;33(3):584–600. doi: 10.1681/ASN.2021081099

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Figure 5. — Combined CUL3 and KLHL3 deficiency causes an FHHt-like phenotype. (A) Western blotting revealed pNCC-T53 and tNCC abundances were significantly higher in Cul3^+/−/Klhl3^+/− mice compared with control mice. (B) Immunofluorescence revealed higher pNCC signal in Cul3^+/−/Klhl3^+/− mice parvalbumin-positive (PV, green) and calbindin-positive (CB, white) cells, consistent with Western blot data. Scale bars: 50 µm. (C) Plasma [K⁺] was significantly higher in Cul3^+/−/Klhl3^+/− mice. (D and E) Radiotelemetric blood pressure measurement revealed no significant difference in SBP was detected on a normal diet, but there was a significantly higher increase in SBP (ΔSBP) in Cul3^+/−/Klhl3^+/− mice fed HS/NK and HS/LK diets compared with control mice (zero in E represents baseline SBP on the day before diet change). (F) Renal clearance showed that Cul3^+/−/Klhl3^+/− mice displayed a greater increase in Na⁺ excretion in response to hydrochlorothiazide administration (HCTZ). Individual values and mean±SEM are shown, with n in parentheses. Statistical differences were examined by two-tailed unpaired t tests (A and C) and two-way repeated measures ANOVA (D). *P<0.05; **P<0.01.