Figure 3. PcKOTsc1 mice show proteinuria and podocyte loss.

(A) Rapamycin treatment prevents proteinuria in PcKOTsc1 mice. Scheme of administration of rapamycin is shown above. Urine (1 μl ) from mice of the indicated genotypes was subjected to SDS-PAGE with Coomassie blue staining (n = 6 each group). veh, vehicle. Asterisk indicates a leak of sample from lane 6. (B) Urinary albumin/creatinine ratio is shown. Urinary albumin and creatinine concentrations in 4-week-old mice were determined by ELISA. *P < 0.001 versus other groups, mean ± SEM, n = 6. Note logarithmic scale for the y axis. Rapamycin treatment was performed from 2 weeks of age as indicated in Figure 2A. (C) TEM analyses reveal abnormal foot process and GBM in PcKOTsc1 and wild-type mice. Representative TEM images of the indicated animals (3 mice/group) from 4 and 8 weeks of age are shown. Rapamycin treatment was as in Figure 2A. Original magnification, ×13,500 (top row), ×7,900 (bottom row). Scale bars: 1 μm. (D) Scanning EM analyses show abnormal podocyte in PcKOTsc1 mice, which was prevented by rapamycin treatment. Rapamycin treatment was as in Figure 2A. Original magnification, ×2,000. Scale bars: 5 μm (top row); 1.25 μm (bottom row). (E) Podocyte loss in PcKOTsc1 mice. The ratio (the number of WT1-positive cells/glomerular tuft area [μm²]) was determined in 15~30 glomeruli from the indicated animals. *P < 0.001 versus wild-type and/or KO with rapamycin treatment, mean ± SEM, n = 3–5 mice.