Summary
Polycystic kidney disease (PKD) is characterized by multiple renal cysts that are lined by epithelium and filled with fluid. PKD may result from one of a number of factors, either inherited or environmental. In this study, we have compared two mouse models in which PKD results from a genetic cause. In the C57BL/6J-cpk model, the mutated gene is unknown. In the other model, an SV40 large T antigen transgene causes renal cysts. We examined cultured cells from the kidneys of these mouse models, comparing growth characteristics. Although several features of PKD lead one to expect that the epithelial cells lining the cysts would have an increased rate of proliferation in culture, we found that they did not. The implications of these findings are discussed.
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References
Avner, E. D. Renal cystic disease. Insights from recent experimental investigations. Nephron 48:89–93; 1988.
Banks-Schiegel, S. P.; Howley, P. M. Differentiation of human epidermal cells transformed by SV40. J. Cell Biol. 96:330–337; 1983.
Brinster, R. L.; Chen, H. Y.; Messing, A., et al. Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 37:367–379; 1984.
Calvet, J. P. Injury and Development in polycystic kidney disease. Curr. Opin. Nephrol. Hypertension 3:340–348; 1994.
Carone, F. A.; Nakamura, S.; Schumacher, B. S. et al. Cyst-derived cells do not exhibit accelerated growth or features of transformed cells in vitro. Kidney Int. 35:1351–1357; 1989.
Colby, W. W.; Shenk, T. Fragments of the simian virus 40 transforming gene facilitate transformation of rat embryo cells. Proc. Natl. Acad. Sci. USA 79:5189–5193; 1982.
Cowley, B. D., Jr.; Chadwick, L. J.; Grantham, J. J., et al. Sequential protooncogene expression in regenerating kidney following acute renal injury. J. Biol. Chem. 264:8389–8393; 1989.
Cowley, B. D., Jr.; Chadwick, L. J.; Grantham, J. J., et al. Elevated protoncogene expression in polycystic kidneys of the C57BL/6J (cpk) mouse. J. Am. Soc. Nephrol. 1:1048–1053; 1991.
Cowley, B. D., Jr.; Smardo, F. L., Jr.; Grantham, J. J., et al. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease. Proc. Natl. Acad. Sci. USA 84:8394–8398; 1987.
Davisson, M. T.; Guay-Woodford, L. M.; Harris, W., et al. The mouse polycystic kidney disease mutation (cpk) is located on proximal chromosome 12. Genomics 9:778–781; 1991.
Gabow, P. A. Polycystic kidney disease: clues to pathogenesis. Kidney Int. 40:989–996; 1991.
Gabriel, K. R. A simple method of multiple comparisons of means. J. Am. Stat. Assoc. 73:724–729; 1978.
Gattone, V. H., II; Calvet, J. P.; Cowley, B. D., Jr., et al. Autosomal recessive polycystic kidney disease in a murine model. Lab. Invest. 59:231–238; 1988.
Gattone, V. H., II; Grantham, J. J. Understanding human cystic disease through experimental models. Seminars Nephrol. 11:617–631; 1991.
Gimbrone, M. A.; Fareed, G. C. Transformation of cultured human vascular endothelium by SV40 DNA. Cell 9:685–693; 1976.
Grantham, J. J. Polycystic kidney disease: neoplasia in disguise. Am. J. Kid. Dis. 15:110–116; 1990.
Grantham, J. J. 1992. Homer Smith Award. Fluid secretion, cellular proliferation, and the pathogenesis of renal epithelial cysts. J. Am. Soc. Nephrol 3:1841–1857; 1993.
Grantham, J. J.; Herron, K. G. An overview of polycystic kidney disease and acquired cystic kidney disease: neoplasia in disguise. Adv. Urol. 3:53–69; 1990.
Harding, M. A.; Chadwick, L. J.; Gattone, V. H., II, et al. The SGP-2 gene is developmentally regulated in the mouse kidney and abnormally expressed in collecting duct cysts in polycystic kidney disease. Dev. Biol. 146:483–490; 1991.
Harding, M. A.; Gattone, V. H., II; Grantham, J. J., et al. Localization of overexpressed c-myc mRNA in polycystic kidneys of thecpk mouse. Kidney Int. 41:317–325; 1992.
Haverty, T. P.; Neilson, E. G. Basement membrane gene expression in polycystic kidney disease. Lab Invest. 58:245–248; 1988.
Kelly, K. A.; Agarwal, N.; Reeders, S., et al. Renal cyst formation and multifocal neoplasia in transgenic mice carrying the SV40 early region. J. Am. Soc. Nephrol. 2:84–97; 1991.
Kleinman, H. K.; McGarvey, M. L.; Liotta, L. A., et al. Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry 21:6188–6193; 1982.
MacKay, K.; Striker, L. J.; Pinkert, C. A., et al. Glomerulosclerosis and renal cysts in mice transgenic for the early region of SV40. Kidney Int. 32:827–837; 1987.
Nadasdy, T.; Laszik, Z.; Lajoie, G., et al. Proliferative activity of cyst epithelium in human renal cystic diseases. J. Am. Soc. Nephrol. 5:1462–1468; 1995.
Pardee, A. B. G1 events and regulation of cell proliferation. Science 246:603–608; 1989.
Preminger, G. M.; Koch, W. E.; Fried, F. A., et al. Murine congenital polycystic kidney disease: a model for studying development of cystic disease. J. Urol. 127:556–560; 1982.
Rankin, C. A.; Grantham, J. J.; Calvet, J. P. c-fos Expression is hypersensitive to serum-stimulation in cultured cystic kidney cells from the C57BL/6J-cpk mouse. J. Cell. Physiol. 152:578–586; 1992.
Russell, E. S.; McFarland, E. C. Cystic kidneys (CK). The Mouse Newsl. 56:40; 1977.
Seshadri, T.; Campisi, J. Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science 247:205–209; 1990.
Stoos, B. A.; Naray-Fejes-Toth, A.; Carretero, O. A., et al. Characterization of a mouse cortical collecting duct cell line. Kidney Int. 39:1168–1175; 1991.
Taub, M. Growth of primary and established kidney cell cultures in serum-free media. In: Barnes, D. W.; Sirbasku, D.; Sato, G., eds. Cell culture methods for molecular and cell biology. Vol. 3. New York Alan R. Liss; 1984:3–24.
Taub, M.; Chuman, L.; Saier, M. H., Jr., et al. Growth of Madin-Darby canine kidney epithelial cell (MDCK) line in hormone-supplemented, serum-free medium. Proc. Natl. Acad. Sci. USA 76:3338–3342; 1979.
Taub, M.; Laurie, G. W.; Martin, G. R., et al. Altered basement membrane protein biosynthesis by primary cultures ofcpk/cpk mouse kidney. Kidney Int. 37:1090–1097; 1990.
Taub, M.; Sato, G. Growth of functional primary cultures of kidney epithelial cells in defined medium. J. Cell. Physiol. 105:369–378; 1980.
Torres, V. E.; Mujwid, D. K.; Johnson, C. M. Proliferative potential of cystderived epithelial cells in ADPKD. J. Am. Soc. Nephrol. 3:303; 1992.
Welling, L. W.; Welling, D. J. Kinetics of cyst development in cystic renal disease. In: Cummings, N. B.; Klahr, S., eds. Chronic renal disease. New York: Plenum; 1985:95–104.
Wilson, P. D.; Hreniuk, D.; Gabow, P. A. Abnormal extracellular matrix and excessive growth of human adult polycystic kidney disease epithelia. J. Cell. Physiol. 150:360–369; 1992.
Wilson, P. D.; Schrier, R. W.; Breckon, R. D., et al. A new method for studying human polycystic kidney disease epithelia in culture. Kidney Int. 30:371–378; 1986.
Wilson, P. D.; Sherwood, A. C. Tubulocystic epithelium. Kidney Int. 39:450–463; 1991.
Ye, M.; Grantham, J. J. The secretion of fluid by renal cysts from patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 329:310–313; 1993.
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Rankin, C.A., Ziemer, D.M., Maser, R.L. et al. Growth characteristics of cells cultured from two murine models of polycystic kidney disease. In Vitro Cell.Dev.Biol.-Animal 32, 100–106 (1996). https://doi.org/10.1007/BF02723041
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DOI: https://doi.org/10.1007/BF02723041