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Kidney Week

Abstract: SA-PO511

Proteomic Differential Study Associated to Autosomal Dominant Polycystic Kidney Disease in Mouse Embryonic Models

Session Information

  • ADPKD: Clinical Studies
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Calviño, Vanesa, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
  • Cordido, Adrian, Instituto de Investigacion Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain
  • Vizoso, Marta, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
  • Bravo, Susana, Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain
  • Diaz-Rodriguez, Candido, University Clinical Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain
  • Garcia-Gonzalez, Miguel A., Health Research Institute of Santiago de Compostela (IDIS)., Santiago de Compostela, GAL, Spain
Background

The autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by the formation of cysts along the nephrons that can lead to renal failure. It is associated with other extrarenal manifestations such as the formation of hepatic or pancreatic cysts, aneurysms, etc. ADPKD is caused by mutations in the PKD1, PKD2 and GANAβ genes. Mouse models of ADPKD with homozygous variants in PKD1 or PKD2 genes present cystogenesis from day 15.5 of gestation and die during embryonic development typically around day 17. The study of these models at embryonic ages could be useful to investigate the molecular mechanisms involved in the onset of cyst formation.

Methods

In order to identify proteins and pathways involved in cystogenesis, we compared the proteome of double mutants vs. healthy mouse embryos kidney. Embryo kidneys were removed at day 15.5 and 16.5 from two animal models of ADPKD with germline mutations in the PKD1 (PKD1del2-4) and PKD2 (PKD2Δ11-13) genes as well as wild type animals. A combined study of two mass spectrometry technologies was carried out: LC-MALDI using a MALDI TOF-TOF 4800 and LC-MS / MS using a MALDI-TripleTOF 6600. The differential proteome of double mutants and healthy mice was identified and their involved pathways were analyzed with Reactome.

Results

We identified 1 protein in E15.5 PKD1 double mutant model not detected in healthy embryo, 6 in E16.5 PKD1, 2 in E15.5 PKD2 and 19 in E16.5 PKD2. We also identified 37 proteins in E15.5 PKD1 models only detected in healthy individuals; 20 in E16.5 PKD1; 20 in E15.5 PKD2 and 5 in E16.5 PKD2. These proteins are involved in different pathways such as metabolism, signal transduction, transcription and immune system as well as development biology, vesicle-mediated transport, hemostasis or cell cycle among others.

Conclusion

Our results would contribute to improve the knowledge on the molecular mechanisms underlying the processes of cystogenesis, as well as to identify possible therapeutic targets.