Clinical Investigation

Kidney International (1995) 48, 496–500; doi:10.1038/ki.1995.319

Gender-dependent disease severity in autosomal polycystic kidney disease of rats

Norbert Gretz, Isabella Ceccherini, Bettina Kränzlin, Ingrid Klöting, Marcella Devoto, Peter Rohmeiss, Berthold Hocher, Rüdiger Waldherr and Giovanni Romeo

Department of Nephrology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany; Laboratory of Molecular Genetics, Istituto Gaslini, Genua, Italy; and Medical Research Center, University of Heidelberg, Klinikum Mannheim, Mannheim, Department of Experimental Diabetes Research, Institute of Diabetes "Gerhardt Katsch", Karlsburg, Department of Nephrology, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Berlin, and Department of Pathology, University of Heidelberg, Heidelberg, Germany

Correspondence: Norbert Gretz MD, Department of Nephrology, University of Heidelberg, Klinikum Mannheim, D-68167 Mannheim, Germany.

Received 12 September 1994; Revised 7 March 1995; Accepted 9 March 1995.

Top

Abstract

Gender-dependent disease severity in autosomal polycystic kidney disease of rats. The impact of gender on the course of chronic renal failure in polycystic kidney disease (PKD) has been under discussion for years. Recently an animal model of autosomal dominant PKD in the rat became available allowing this topic to be studied. The aim of this study was to evaluate disease severity according to gender, and the occurrence of anticipation and/or genetic imprinting. Male and female affected PKD rats were crossed with respective Wistar-Ottawa-Karlsburg (WOK) rats. From this P generation 26 affected F1 hybrids were obtained, which were then backcrossed with WOK rats, resulting in 275 backcrosses (BC generation). In BC rats the affected males had a significantly higher kidney weight, worse histology and poorer renal function than the females. In the male, but not the female rats of the BC generation, transmission from an affected F1 mother resulted in significantly higher kidney weight, worse histology and poorer renal function than when the gene was inherited through an affected father. Since at the same time body and kidney weight were higher in the respective unaffected males, the previous effect in the affected rats might be due to a growth factor transferred by the mother's milk. The sex of the P generation had no such impact on these parameters. Thus our data provide no evidence for disease anticipation and genetic imprinting (in the classical sense) in the PKD rats, and the assumption of a gender-dependent disease expressivity is favored.

Top

References

  1. Gretz N, Zeier M, Geberth S, Strauch M, Ritz E: Is gender a determinant for the evolution of renal failure? A study in adult dominant polycystic kidney disease. Am J Kidney Dis 14:178–183, 1989 | PubMed | ISI | ChemPort |
  2. Disney APS: 10th Report of the Australian and New Zealand Combined Dialysis and Transplant Registry (ANZDATA).. 1987
  3. Stewart JH: End-stage renal failure appears earlier in men than in women with polycystic kidney disease. Am J Kidney Dis 24:181–183, 1994 | PubMed |
  4. Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, Jones RH: Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int 41:1311–1319, 1992 | PubMed | ISI | ChemPort |
  5. Bear JC, Parfrey PS, Morgan J, Martin C, Cramer B: Autosomal dominant polycystic kidney disease: New information for genetic counseling. Am J Med Genet 45:548–553, 1992
  6. Fick GM, Johnson AM, Gabow PA: Is there evidence for anticipation in autosomal-dominant polycystic kidney disease? Kidney Int 45:1153–1162, 1994 | PubMed | ISI | ChemPort |
  7. Kaspareit-Rittinghausen J, Rapp K, Deerberg F, Wcislo A, Messow C: Hereditary polycystic kidney disease associated with osteorenal syndrome in rats. Vet Pathol 26:195–201, 1989 | PubMed | ChemPort |
  8. Kaspareit-Rittinghausen J, Deerberg F, Rapp K, Messow C, Wcislo A: Untersuchung an einer Han:SPDR-Rattenmutante mit polycystischen Nieren, Urämie und osteorenalem Syndrom. Dtsch tierärztl Wschr 96:397–432, 1989
  9. Cowley BD Jr, Gudapaty S, Kraybill AL, Barash BD, Harding MA, Calvet JP, Gattone VH II: Autosomal-dominant polycystic kidney disease in the rat. Kidney Int 43:522–534, 1993 | PubMed | ISI |
  10. Gretz N, Hocker A, Baur S, Lasserre JJ, Bachmann S, Waldherr R, Strauch M: Rat models of polycystic kidnev disease. Contrib Nephrol 97:35–46, 1992 | PubMed | ChemPort |
  11. Kaspareit-Rittinghausen J, Deerberg F, Rapp K, Wcislo A: A new rat model for polycystic kidney disease of humans. Transplant Proc 22:2582–2583, 1990
  12. Schäfer K, Gretz N, Bader M, Oberbäumer I, Eckhardt KU, Kriz W, Bachmann S: Characterization of the Ham:SPRD rat model for hereditary polycystic kidney disease. Kidney Int 46:134–152, 1994 | PubMed | ISI | ChemPort |
  13. Schäfer K, Bader M, Gretz N, Oberbäumer I, Bachmann S: Focal overexpression of collagen IV characterizes the initiation of epithelial changes in polycystic kidney disease. Exper Nephrol 2:190–195, 1994
  14. Bachmann S, Ramasubbu K, Schäfer K, Uiker S, Gretz N: Tubulo-interstitial changes in the HAN:SPRD rat model for autosomal dominant polycystic kidney disease. Contrib Nephrol (in press)
  15. Gretz N, Haisch S, Baur S, Bauss F, Bachmann S, Waldherr R, Strauch M: Models of polycystic kidney disease in the rat, in Experimental and Genetic Rat Models of Chronic Renal Failure, edited by N Gretz, M Strauch, Basel, Karger, 1993, pp 115–123
  16. Gretz N: Accelerated renal death following unilateral nephrectomy in a rat strain with autosomal dominant polycystic kidney disease. JASN 4:1925–1926, 1994
  17. Kaspareit-Rittinghausen J, Deerberg F, Rapp K, Wcislo A: Renal hypertension in rats with hereditary polycystic kidney disease. Z Versuchstierkd 33:201–204, 1990 | PubMed | ChemPort |
  18. Kaspareit-Rittinghausen J, Deerberg F, Wcislo A: Adult polycystic kidney disease associated with renal hypertension, renal osteodystrophy, and uremic enteritis in SPRD rats. Am J Pathol 139:693–696, 1991 | PubMed | ChemPort |
  19. Gretz N: Progression of chronic renal failure in a rat strain with autosomal dominant polycystic kidney disease. Nephron 68:462–467, 1994 | PubMed | ISI | ChemPort |
  20. Klöting I, Vogt L: Rat strains maintained at the Central Institute of Diabetes. Rat Newsletter 21:20–21, 1989
  21. SAS/STAT User's Guide. ACECLUS-FREQ., Release 6.04 edition, Cary, SAS Institute Inc., 1990
  22. SAS/GRAPH Software (vol 2). Release 6 edition, Cary, SAS Institute Inc., 1990
  23. SAS/STAT User's Guide (vol 2). GLM-VARCOMP, Release 6.04 edition, Cary, SAS Institute Inc., 1990
  24. SAS Procedures Guide. Version 3 edition, Cary, SAS Institute Inc., 1987
  25. Zerres K, Rudnik-Schöneborn S: On genetic heterogeneity, anticipation, and imprinting in polycystic kidney diseases. Nephrol Dial Transplant 10:7–9, 1995
  26. Fick GM, Johnson AM, Strain JD, Kimberling WJ, Kumar S, Manco-Johnson ML, Duley IT, Gabow PA: Characteristics of very early onset autosomal dominant polycystic kidney disease. JASN 3:1863–1870, 1993
  27. Zerres K, Rudnik-Schöneborn S, Deget F: Childhood onset autosomal dominant polycystic kidney disease in sibs: clinical picture and recurrence risk. German Working Group on Paediatric Nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie). J Med Genet 30:583–588, 1993 | PubMed | ISI | ChemPort |
  28. Torra R, Darnell A, Botex A, Estivill X, Revert LI: Interfamilial and intrafamilial variability of clinical expression in autosomal dominant polycystic kidney disease. (abstract) JASN 5:653, 1994
  29. Hall JG: Genomic imprinting: Review and relevance to human diseases. Am J Hum Genet 46:857–873, 1990 | PubMed | ISI | ChemPort |
  30. Caskey CT, Pizzuti A, Fu YH, Fenwick RG Jr, Nelson DL: Triplet repeat mutations in human disease. Science 256:784–789, 1992 | Article | PubMed | ISI | ChemPort |
  31. Mandel JL: Trinucleotide diseases on the rise. Nature Genet 7:453–455, 1994 | Article |
  32. Lakshmanan J, Eysselein V: Hereditary error in epidermal growth factor prohormone metabolism in a rat model of autosomal dominant polycystic kidney disease. Biochem Biophys Res Commun 197:1083–1093, 1993 | Article | PubMed | ISI | ChemPort |
  33. Thulesen J, Poulsen SS, Nexo E, Raaberg L: Epidermal growth factor in rat milk is dependent on insulin. Endocrine Reg 27:139–144, 1993
  34. Roa RK, Lam K, Philipps AF, Williams C, Lake M, Koldovsky O: Presence of multiple forms of peptidase inhibitors in rat milk. J Pediatr Gastroenterol Nutr 17:414–420, 1993
  35. Thulesen J, Nexo E, Raaberg L, Poulsen SS: Decreased level of epidermal growth factor in milk from diabetic rats. Pediatr Res 35:107–111, 1994
  36. Hiramatsu M, Kashimata M, Takayama F, Minami N: Developmental changes in and hormonal modulation of epidermal growth factor concentration in the rat submandibular gland. J Endocrinol 140:357–363, 1994
  37. Kreisberg JL, Karnovsky MJ: Focal glomerular sclerosis in the fawnhooded rat. Am J Pathol 92:637–652, 1978 | PubMed | ISI | ChemPort |
  38. Rudofsky UH, Magro AM: Spontaneous hypertension in fawnhooded rats. Lab Animal Sci 32:389–391, 1982
  39. Zeier M, Gretz N: The influence of gender on the progression of renal failure, in Experimental and Genetic Rat Models of Chronic Renal Failure, edited by N Gretz, M Strauch, Basel, Karger, 1993, pp 250–257

Extra navigation

.
ADVERTISEMENT