title: Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms.
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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Hughes
authors.forename: M
authors.initials: M
authors.lastname: Robati
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.forename: P
authors.initials: P
authors.lastname: Bouillet
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D005260:Female; D005838:Genotype; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050396:TRPP Cation Channels; C000606776:Bcl2l11 protein, mouse