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. 2011 May 23;121(6):2181–2196. doi: 10.1172/JCI44771

Figure 5. mTORC1 activation in podocytes causes proteinuria and mesangial expansion in adult mice.

Figure 5

(A) Rapamycin prevents death in PcKOTsc1 mice. Mice were treated with rapamycin as indicated. Survival curve of the indicated animals is shown. Wild-type, n = 50; heterozygous (Het), n = 50; KO, n = 50; KO with rapamycin treatment (off-on), n = 15; KO with rapamycin treatment (off-on-off), n = 10; KO C57BL/6 (B6) background, n = 30. (B) mTORC1 activation in podocytes causes proteinuria and mesangial expansion in adult mice. Withdrawal of rapamycin treatment in adult PcKOTsc1 mice led to rapid onset of proteinuria and glomerulopathy. Scheme of administration of rapamycin is shown at top. Urinary albumin concentrations of the indicated animals were determined (WT 4 wk; KO 15 wk [rapamycin treatment from 2 to 15 weeks]; KO 16 wk, 19 wk, and 21 wk [off-on-off; 1 wk, 4 wk, and 6 wk after withdrawal of rampamycin treatment]). *P < 0.001 versus WT and KO 15 wk, mean ± SD, n = 6. (C) Withdrawal of rapamycin treatment in adult PcKOTsc1 mice led to mesangial expansion. Scheme of administration of rapamycin is shown at top. H&E and PAS staining of the representative glomeruli are shown. PAS-positive area in glomerulus was measured in 30 glomeruli from the indicated animals. *P < 0.001 versus other groups, n = 4. Original magnification, ×400.