Rapamycin attenuates lymphatic hyperplasia and restores lymphatic function in Prox1-CreER^T2;LSL-Pik3ca^H1047R mice. (A) Schematic that shows when mice were injected with tamoxifen. Prox1-CreER^T2;LSL-Pik3ca^H1047R mice were treated with vehicle or rapamycin (100 μg; 5×/wk) from P70 to P91. Tam, tamoxifen. (B and C) Representative images of ear skin whole-mounts stained with an anti–Lyve-1 antibody. (D) Lymphatic vessel index values were significantly higher in vehicle-injected mice (273 ± 5.404, n = 6) than in rapamycin-injected mice (192.5 ± 6.876, n = 7). (E and F) EBD was transported to the iliac lymph nodes in most rapamycin-treated mice (9 out of 11 mice). In contrast, EBD was not transported to the iliac lymph nodes in vehicle-treated mice (n = 9). ****, P < 0.0001; unpaired Student’s t test). Bars, 100 µm.