Skip to main content
SpringerLink
Log in

Congenital murine polycystic kidney disease

I. The ontogeny of tubular cyst formation

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

In the current study, the ontogeny of tubular cyst formation was studied in the CPK mouse, a murine strain with autosomal recessive polycystic kidney disease. Utilizing the technique of intact nephron microdissection in addition to standard light and transmission electron microscopy, the earliest morphologic alterations in CPK kidneys were localized in fetal tissue at 17 days of gestation to the distal portion of developing proximal tubules. During disease progression, from birth to 21 days of postnatal age, there was a shift in the site of cystic nephron involvement from proximal tubule to collecting tubules without involvement of other nephron segments. Cysts were enlarged tubular segments which remained in continuity with other portions of the nephron and were not associated with abnormalities in the overall pattern of nephron growth or differentiation. Analysis suggested that alterations in transtubular transport in abnormally shortened proximal tubular segments of juxtamedullary nephrons may have pathogenic importance in the early stages of cyst formation, and that epithelial hyperplasia and cytoskeletal alterations may have a role in progressive proximal tubular cystic enlargement. Cellular hyperplasia of epithelial walls of normally formed tubules was a prominent feature of cyst formation and progressive enlargement in collecting tubules. Such data form the basis for future studies into specific pathophysiological processes which may be operative in specific nephron segments during different stages of cyst formation in the CPK mouse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zerres K, Volpel MC, Weiss H (1984) Cystic kidneys: genetics, pathologic anatomy, clinical picture, and prenatal diagnosis. Hum Genet 68:104–135

    PubMed  Google Scholar 

  2. Welling LW, Grantham JJ (1986) Cystic and developmental diseases of the kidney. In: Brenner BM, Rector FC (eds) The kidney, 3rd ed. Saunders, Philadelphia, p 1341–1376

    Google Scholar 

  3. Grantham JJ (1983) Polycystic kidney disease: a predominance of giant nephrons. Am J Physiol 244:F3-F10

    PubMed  Google Scholar 

  4. Broyer MD (1984) Incidence and etiology of ESRD in children. In: Fine RN, Gruskin AB (eds) End stage renal disease in children. Saunders, Philadelphia, p 9–16

    Google Scholar 

  5. Avner ED (1987) Polycystic kidney disease: insights from recent experimental investigations. Nephron 43: (in press)

  6. Russell ES, McFarland EC (1977) Cystic kidneys. Mouse Newslett 56:40–43

    Google Scholar 

  7. Preminger GM, Koch WE, Fried FA, McFarland E, Murphy ED, Mandell J (1982) Murine congenital polycystic kidney disease: a model for studying development of cystic disease. J Urol 127:556–560

    PubMed  Google Scholar 

  8. Nidess R, Koch WE, Fried FA, McFarland E, Mandell J (1984) Development of the embryonic murine kidney in normal and congenital polycystic kidney disease: characterization of a proximal tubular degenerative process as the first observable light microscopic defect. J Urol 131: 156–162

    PubMed  Google Scholar 

  9. Oliver J, MacDowell M (1961) The structural and functional aspects of the handling of glucose by the nephrons and the kidney and their correlation by means of structural-functional equivalents. J Clin Invest 40:1093–1112

    PubMed  Google Scholar 

  10. Fetterman GH, Shuplock NA, Philipp FJ, Gregg HS (1965) The growth and maturation of human glomeruli and proximal convolutions from term to adulthood. Pediatrics 35:601–619

    PubMed  Google Scholar 

  11. Fetterman GH, Fabrizio NS, Studnicki FM (1969) Microdissection of the nephron: The method and its applications. In: Sunderman FW, Sunderman FW Jr (eds) Laboratory diagnosis of kidney disease. Green, St. Louis, p 32–45

    Google Scholar 

  12. Sokal RR, Rohlf FJ (1969) Biometry: the principles and practice of statistics in biological research. Freeman, San Francisco, pp 11–229

    Google Scholar 

  13. Osathanondh V, Potter EL (1964) Pathogenesis of polycystic kidneys. Arch Pathol 77:466–473

    PubMed  Google Scholar 

  14. Baxter TJ (1965) Polycystic kidney of infants and children. Morphology, distribution, and relation of the cysts. Nephron 2:15–31

    Google Scholar 

  15. Heggo O, Natvig JB (1965) Cystic disease of the kidneys. Acta Pathol Microbiol Scand 63:500–512

    Google Scholar 

  16. Kanwar YS, Carone FA (1984) Reversible changes of tubular cell basement membrane in drug-induced renal cystic disease. Kidney Int 26:35–43

    PubMed  Google Scholar 

  17. Gardner KD, Evan AP, Reed WP (1986) Accelerated renal cyst development in deconditioned germ-free rats. Kidney Int 29:116–1123

    Google Scholar 

  18. Avner ED, Sweeney WE, Piesco NP, Ellis D (1986) Regression of genetically-determined polycystic kidney disease in murine organ culture. Experientia 42:77–80

    PubMed  Google Scholar 

  19. Larsson L (1975) Effects of different fixatives on the ultrastructure of the developing proximal tubule in the rat kidney. J Ultrastruct Res 51:140–148

    PubMed  Google Scholar 

  20. Bentzel CJ, Parsa B, Hare DK (1969) Osmotic flow across proximal tubule of necturus: correlation of physiologic and anatomic studies. Am J Physiol 217:570–580

    PubMed  Google Scholar 

  21. Spring KR, Hope A (1978) Size and shape of the lateral intercellular spaces in a living epithelium. Science 200: 54–58

    PubMed  Google Scholar 

  22. Larsson L (1980) Correlation of ultrastructure and fluid transport in developing proximal tubules. In: Maunsbach AB, Olsen TS, Christensen EI (eds) Functional ultrastructure of the kidney. Academic Press, New York, p 223–237

    Google Scholar 

  23. Maunsbach AB, Boulpaep EL (1983) Paracellular shunt ultrastructure and changes in fluid transport in necturus proximal tubule. Kidney Int 24:610–619

    PubMed  Google Scholar 

  24. Avner ED, Piesco NP, Sweeney WE, Studnicki FM, Fetterman GH, Ellis DE (1984) Hydrocortisone-induced cystic metanephric maldevelopment in serum-free organ culture. Lab Invest 50:208–218

    PubMed  Google Scholar 

  25. Avner ED, Sweeney WE, Finegold DN, Piesco NP, Ellis D (1985) Sodium-potassium ATPase activity mediates cyst formation in metanephric organ culture. Kidney Int 28: 447–455

    PubMed  Google Scholar 

  26. Avner ED, Sweeney WE, Piesco NP, Ellis D (1987) Triiodothyronine induced cyst formation in metanephric organ culture. The role of increased Na−K ATPase activity. J Lab Clin Med 109:441–454

    PubMed  Google Scholar 

  27. Rozen R, Scriver CR, Mohyuddin F (1983) Hypertaurinuria in the C57BL/6J mouse: altered transport at the renal basolateral membrane. Am J Physiol 244:F150-F155

    PubMed  Google Scholar 

  28. Crocker JFS, Blecher SR, McCarthy SC (1987) Polycystic kidney and liver disease and corticosterone changes in the CPK mouse. Kidney Int 31:1088–1091

    PubMed  Google Scholar 

  29. Malick LE, Lagenbach K (1976) Scanning electron microscopy of in vitro chemically transformed mouse embryo cells. J Cell Biol 68:654–664

    PubMed  Google Scholar 

  30. Meek WD, Davis WL (1986) Cytochalasin D and cationized ferritin as probes for the morphological investigation of blebbing in two human cell lines. In Vitro Cell Dev Biol 22:725–737

    PubMed  Google Scholar 

  31. Porter K, Prescott D, Frye J (1973) Changes in surface morphology of Chinese hamster ovary cells during the cell cycle. J Cell Biol 57:815–836

    PubMed  Google Scholar 

  32. McCrory WW (1972) Developmental nephrology. Harvard University Press, Cambridge

    Google Scholar 

  33. Oliver J (1968) Nephrons and kidneys. Harper & Row, New York

    Google Scholar 

  34. Gardner KD Jr, Solomon S, Fitzgerrel WE, Evan AP (1976) Function and structure in the diphenylamine-exposed kidney. J Clin Invest 57:796–806

    PubMed  Google Scholar 

  35. Evan AP, Gardner KD Jr (1979) Nephron obstruction in nordihydroguaiaretic acid-induced renal cystic disease. Kidney Int 15:7–19

    PubMed  Google Scholar 

  36. Evan AP, Gardner KD Jr, Bernstein J (1979) Polypoid and papillary epithelial hyperplasia: a potential cause of ductal obstruction in adult polycystic disease. Kidney Int 16:743–750

    PubMed  Google Scholar 

  37. Evan AP, Gardner KD Jr (1985) Morphology of polycystic disease in man and experimental models. In: Cummings NB, Klahr S (eds) Chronic renal disease. Plenum Press, New York, p 55–68

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics (Nephrology) and Pathology, the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Ellis D. Avner, Frances E. Studnicki, Michael C. Young, William E. Sweeney Jr, Nicholas P. Piesco, Demetrius Ellis & George H. Fettermann

  2. Department of Anatomy/Histology, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania, USA

    Ellis D. Avner, Frances E. Studnicki, Michael C. Young, William E. Sweeney Jr, Nicholas P. Piesco, Demetrius Ellis & George H. Fettermann

Authors
  1. Ellis D. Avner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frances E. Studnicki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael C. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William E. Sweeney Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicholas P. Piesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Demetrius Ellis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. George H. Fettermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avner, E.D., Studnicki, F.E., Young, M.C. et al. Congenital murine polycystic kidney disease. Pediatr Nephrol 1, 587–596 (1987). https://doi.org/10.1007/BF00853593

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00853593

Key words

Search

Navigation