Figure 11. KCTD1 but not KCTD15 is required for renal function.

(A) Kctd15 is expressed in the kidney mainly in medullary collecting ducts, whereas Kctd1 is expressed in all distal nephron segments. X-gal staining in adult kidneys of Kctd1^Lacz/WT and Kctd15^Lacz/WT mice. (B) Six2Cre⁺Kctd1^fl/fl mice show elevated blood urea nitrogen (BUN), whereas inactivation of KCTD15 in the kidney during development or in the adult does not affect renal function. Inducible inactivation of KCTD15 in all cells (β-actin-CreERT2⁺Kctd15^fl/fl mice [iKctd15 KO] treated with tamoxifen [TAM] at 3 months of age and assessed at 11 months of age) does not increase BUN. Mean ± SEM; P values (Mann-Whitney test). (C) Interstitial fibrosis in kidneys of Kctd1^–/–Col1GFP⁺ mice (green, type I collagen). Seven-month-old Kctd1^–/–Col1GFP⁺ and Kctd1^–/WTCol1GFP⁺ mice. Scale bars: 10 μm. (D) Normal kidney morphology in adult Aqp2Cre⁺Kctd1^fl/flKctd15^fl/fl mice, Aqp2Cre⁺Kctd15^fl/fl mice, Nphs2Cre⁺Kctd15^fl/fl mice, or Six2Cre⁺Kctd15^fl/fl mice. Adult (3-month-old) Six2Cre⁺Kctd1^fl/fl mice show abnormal and dilated distal nephron segments in the kidney cortex (red arrows). (E) DEGs in P8 kidneys of Six2Cre⁺Kctd1^fl/fl mice and their nephron segment location (compared with P8 controls). DEGs of whole-kidney bulk RNA-Seq defined by: FDR < 0.01; log₂(fold change) > 1; log₂(CPM) > 1. CPM, counts per million. (F) Significantly upregulated pathways according to GSEA in P8 kidneys of Six2Cre⁺Kctd1^fl/fl mice include “epithelial structure maintenance” and “anion transmembrane transport.” NES, normalized enrichment score.