Fig. 4

Podocyte GSK3 loss activates Wnt-β-catenin but this is not responsible for pathology. a β-catenin is expressed in podocytes and throughout the kidney in podGSK3DKO and mpodGSK3DKO mice but not in single isoform podocyte-specific knockout mice. Representative IHC pictures, scale bar = 25 μm. b Western blot of kidney lysates shows increased activated β-catenin in podGSK3DKO mice but not in control and single isoform podocyte-specific knockout mice, n = 3 experiments. See also Supplementary Fig. 5a. (c) No difference in survival of the podGSK3DKO/β-catenin KO compared to the podGSK3DKO mice. (Kaplan–Meier survival curve. Log-rank (Mantel-Cox test non-significant) podGSK3DKO n = 14; podGSK3DKO/β-catenin KO n = 12 mice. d No difference in the histological appearance of the podGSK3DKO/β-cateninKO compared to the podGSK3DKO mice at day 10 of life. Representative images of PAS staining, scale bar = 25 μm. e No difference in the level of albuminuria in podGSK3DKO/β-cateninKO compared to the podGSK3DKO mice. (Cre negative control n = 10; podGSK3DKO n = 10; podGSK3DKO/β-catenin KO n = 7 mice. Kruskel Wallis test not significant). f No difference in the level of albuminuria in mpodGSK3DKO/β-cateninKO compared to the mpodGSK3DKO mice, n = 5–7. g Inhibiting the Wnt pathway has no effect on cipodGSK3DKO cell survival (n = 3 experiments). h Inhibiting the Notch pathway has no effect on cipodGSK3DKO cell survival (n = 3 experiments). i Inhibiting the Hedgehog pathway in cipodGSK3DKO cells increases cell death (unpaired two-tailed t test *p < 0.05, n = 3 experiments). Data are presented as the mean ± SEM