Fig. 4. Pkd2 derepression retards cyst growth in Pkd1-mutant models.

a Immunoblot showing Polycystin-2 (PC2) expression in cells with the indicated genotypes. miR-17 motif deletion from Pkd2 3′-UTR leads to higher PC2 expression in Pkd1^RC/- cells. Actin serves as the loading control. #1 and #2 refer to the two independent Pkd1^RC/-; Pkd2^Δ17/Δ17 clonal cell lines. n = 3 biologically independent samples for both clones. b, c Representative images and quantification showing 3D cyst size of cells with indicated genotypes grown in Matrigel cultures. n = 300 cysts pooled from three independent experiments. d Representative images showing mitotracker labeling and anti-pCreb1 immunostaining in cells with the indicated genotypes. n = 3 biologically independent experiments. e Heatmap showing alamarBlue-assessed proliferation of Pkd1^RC/- and Pkd1^RC/-; Pkd2^Δ17/Δ17 cells in the absence (−) or presence (+) of cAMP, glucose, or SAM. n = 8, each circle represents a biological replicate. f H&E-stained kidney sections from 18-day-old mice with the indicated genotypes are shown. n = 3 (Pkd1^RC/+; Pkd2^+/+), n = 3 (Pkd1^RC/+; Pkd2^∆17/∆17), n = 8 Pkd1^RC/-; Pkd2^+/+), and n = 11 (Pkd1^RC/-; Pkd2^∆17/∆17). g Immunoblots showing PC2, Yap1, and c-Myc expression in kidneys of 18-day-old mice with the indicated genotypes (n = 3 for each group). h, i KW/BW and serum creatinine levels in 18-day-old mice with the indicated genotypes. j Representative images showing pHH3 and MRC1 immunostaining in kidney sections from 18-day-old mice with the indicated genotypes (n = 3 for each group). k Heatmap showing differential mRNA expression in kidneys of 18-day-old mice with the indicated genotypes (n = 3). mRNAs that were dysregulated in Pkd1^RC/- compared to Pkd1^RC/+ kidneys but exhibited improved expression in Pkd1^RC/-; Pkd2^Δ17/Δ17 kidney were chosen for heatmap visualization. Error bars indicate SEM. Statistical analysis: One-way ANOVA, Tukey’s multiple-comparisons test (b, h, and i). Source data are provided as a Source Data file.