Normal kidney histology and function are observed in cDKO mice within 3 months of doxycycline induction. (A) Ocrl, Inpp5b, Pax8rtTA, and TetO-cre genotypes confirmed by tail genotyping. (B) Expression of OCRL in control, Ocrl KO, and cDKO renal cortex by immunoblot. (C) Inpp5b mRNA expression in control, Ocrl KO, and cDKO renal cortex by RT-PCR. *P<0.05 (n=3). (D) Representative low–power images of H&E–, periodic acid–Schiff (PAS)–, and trichrome–stained kidney sections from control, Ocrl KO, and cDKO mice. Interstitial fibrosis (arrowheads) is observed in cDKO mice kidneys at 8 months after doxycycline induction when stained with trichrome. Scale bars, 50 μm. (E) Quantification of interstitial fibrosis in control, Ocrl KO, and cDKO at 1, 3, and 8 months after doxycycline induction. *P<0.05 (n=3). (F) cDKO mice show elevated plasma creatinine 8 months after doxycycline induction. *P<0.05 (n=4). (G and H) Isolated renal brush border samples from control, Ocrl KO, and cDKO mice kidneys at (G) 1 and (H) 3 months after doxycycline induction immunoblotted with megalin, NaPi2a, and NHE3 antibodies. (I–K) Quantification by densitometry of the immunoblots of proteins in H. *P<0.05 (n=3).