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. 2006 Jul;13(7):1123-7.
doi: 10.1038/sj.cdd.4401815. Epub 2005 Nov 11.

Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms

P Hughes  1 , M Robati, W Lu, J Zhou, A Strasser, P Bouillet
Affiliations

Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms

P Hughes et al. Cell Death Differ. 2006 Jul.

Abstract

We have recently demonstrated that ablation of one or both alleles of the proapoptotic gene Bim prevents the polycystic kidney disease (PKD) that develops in mice deficient for the prosurvival protein Bcl-2. The aim of the present study was to investigate whether loss of Bim or Bcl-2 could influence the disease in the PKD1del34/del34 mutant mice, a model of autosomal dominant PKD. PKD1del34/del34 mice were intercrossed with Bim-deficient mice and Bcl-2+/- mice to generate double mutants. Loss of Bim does not prevent the development of PKD in PKD1del34/del34 mice. On the C57BL/6 genetic background, most older PKD1del34/+ mice do not develop PKD, but present with liver cysts. Surprisingly, loss of Bim completely prevented liver cysts formation in PKD1del34/+ mice. Loss of one Bcl-2 allele did not influence the PKD1del34 phenotype significantly. We conclude that loss of PKD1 and loss of Bcl-2 elicit PKD through distinct mechanisms.

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Figures

Figure 1
Figure 1
Loss of Bim does not rescue polycystic kidney disease in PKD1del34/del34 mice. Bim−/−/PKD1del34/del34 newborn mice display the same phenotype as Bim+/+/PKD1del34/del34 pups
Figure 2
Figure 2
Kidney morphology. Kidneys of wild-type (wt), Bim−/−/PKD1+/+, Bim−/−/PKD1del34/+ and Bim−/−/PKD1del34/del34 newborn mice are compared. Magnification ×50
Figure 3
Figure 3
Older Bim and PKD1del34 mice. (a) Kidneys of all 14–16 month-old Bim−/− mice present with lymphocyte infiltrates rarely seen in the other genotypes considered here. Bar, 1 mm. (b) Unlike Bim+/+/ PKD1del34+/− mice, Bim−/−/PKD1del34+/− and Bim−/−/PKD1+/+ do not develop liver cysts upon ageing. Bar, 1mm
Figure 4
Figure 4
Different manifestations of PKD in Bcl-2−/− and PKD1del34/del34 mice. Kidneys of Bcl-2−/− (b, e) and PKD1del34/del34 (c, f) were compared with wt (a, d). Haematoxylin/eosin-stained kidney sections of E15.5 embryo (a–c) and newborn mice (d–f). Bcl-2−/− kidneys are smaller but do not show any cyst at birth, whereas PKD1del34/del34 kidneys are larger and show cysts throughout development. Magnification ×50
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References

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