Ralph Witzgall, Bettina Kränzlin, Norbert Gretz, Nicholas Obermüller 

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Impaired endocytosis may represent an obstacle to gene therapy in polycystic kidney disease  Ralph Witzgall, Bettina Kränzlin, Norbert Gretz, Nicholas Obermüller  Kidney International  Volume 61, Issue 1, Pages S132-S137 (January 2002) DOI: 10.1046/j.1523-1755.2002.0610s1132.x Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 1 Location of renal cysts in the (cy/+) rat model of ADPKD. Histochemical staining of a kidney section from a (cy/+) rat for alkaline phosphatase, a marker enzyme of the proximal tubule, leads to the convenient identification of proximal tubules. On this overview it can be easily seen that most cysts are derived from proximal tubules located in the cortex. It is likely that the unstained cysts nevertheless have originated from proximal tubules, but have lost alkaline phosphatase in the course of cyst formation. Bar, 400 μm. Kidney International 2002 61, S132-S137DOI: (10.1046/j.1523-1755.2002.0610s1132.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 2 Endocytosis of FITC-labeled dextran by non-cystic proximal tubules. Systemically administered FITC-labeled dextran is readily taken up by the kidney. At a higher magnification, a punctate pattern of FITC-dextran labeling can be seen, which represents the newly formed endosomes in cortical proximal tubules. Bar, 25 μm. Kidney International 2002 61, S132-S137DOI: (10.1046/j.1523-1755.2002.0610s1132.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 3 FITC-dextran uptake and ClC-5 protein expression in cyst-lining epithelial cells. A cyst from a cortical kidney section of a 16 week-old (cy/+) rat injected with FITC-labeled dextran shows a mosaic distribution of FITC-dextran uptake (a). Immunofluorescence staining with an antibody against ClC-5 (b) demonstrates that those cells, which do not endocytose FITC-dextran any longer, also do not express ClC-5. The corresponding interference phase-contrast view is shown in c. Bar, 20 μm. Kidney International 2002 61, S132-S137DOI: (10.1046/j.1523-1755.2002.0610s1132.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 4 FITC-dextran uptake and megalin expression in cyst-lining epithelial cells. Two cysts from a cortical kidney section of a 16 week-old (cy/+) rat injected with FITC-labeled dextran show a mosaic distribution of FITC-dextran uptake (a). Immunofluorescence staining with an antibody against megalin (b) demonstrates that those areas, which do not endocytose FITC-dextran any longer, also do not express megalin. The corresponding interference phase-contrast view is shown in c. Bar, 25 μm. Kidney International 2002 61, S132-S137DOI: (10.1046/j.1523-1755.2002.0610s1132.x) Copyright © 2002 International Society of Nephrology Terms and Conditions