TWEAK treatment during a noncystic window accelerates cyst formation. (A) Representative hematoxylin and eosin–stained kidney sections from TWEAK (n=4) and control (n=6) mice (Pkd1cond/cond;Tam-Cre+), with Pkd1 deletion induced at p15–16 and mice euthanized at p30. Schematic representation of the experimental design provided in Supplemental Figure 1A. Several cysts (Cy) are observed in a focal distribution pattern in TWEAK-treated kidneys. Arrows represent dilated tubules. Scale bars, 2 mm (upper panel) and 100 µm (lower panel). Renal function assessed by (B) BUN and the (C) kidney/body weight ratio do not change significantly. In contrast, TWEAK increased (C) the cystic index and (E) the number of cysts. (F) Immunofluorescence for specific nephron markers from proximal tubule (LTL, green, upper panel), ascending limb of the loop of Henle (THP, red, center), and collecting duct (DBA, red, lower panel). *Cyst without specific marking; yellow arrow, dilated tubule; yellow arrowhead, tubule. Scale bars, 50 µm (upper panel) and 100 µm (center and lower panels). Bars represent means±SEM. *P<0.05. DAPI, 4′,6-diamidino-2-phenylindole.