Figure 2.
Cyst-specific nuclear translocation of transcription factor EB (Tfeb) and transcription factor E3 (Tfe3) and the activation status of mammalian target of rapamycin complex 1 (mTORC1). Serial renal formalin-fixed paraffin-embedded sections derived from folliculin (Flcn)fl/fl:Ksp-Cre [Flcn knockout (KO); A–C], folliculin-interacting protein (Fnip)1fl/fl:Fnip2fl/flKsp-Cre [Fnip1/2 double KO (dKO); D–F], or control (G–I) animals were subjected to immunohistochemistry using antibodies raised against Tfeb (A, D, and G), Tfe3 (B, E, and H), or phosphorylated (p)-S6 (Ser235/236; C, F, and I). Nuclear Tfe3 was detected in most cystic epithelial cells in both models (B and E) compared with control (H) renal epithelia, which showed no evidence of nuclear translocation. Activation of mTORC1, as assessed by p-S6 (Ser235/236; C and F), displayed a sporadic and patchy staining pattern in tissue sections from cystic kidneys in which nuclear Tfeb and Tfe3 staining was predominant. Scale bars = 50 µm; scale bars in insets = 10 µm. Images are representative of five ×20 images acquired from three separate animals for each genotype. P18, postnatal day 18.