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Abstract: PO1528

Collagen Changes Suggestive of a Primary Defect in pkd2+/- Adult Zebrafish Kidney

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Addani, Mohamed Ahmed, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Anaam, Deema A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Alzamareh, Diana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Modawi, Abdalla A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ho, Nicole, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Webb, Kevin L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Holmes, Heather L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Romero, Michael F., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Macura, Slobodan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sussman, Caroline R., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Zebrafish are a valuable model for studies of PKD, with conservation of pathways and phenotypes including renal cysts. Pkd2 mutant zebrafish develop dorsal tail curvature (pkd2-/-), which prevents survival. No phenotype has been described in pkd2+/- zebrafish embryos or adults. MRI is useful for analysis of PKD kidney and collagen changes characterize PKD. In this study, we examined collagen changes in pkd2+/- adult zebrafish kidney and MRI in vivo.

Methods

Zebrafish hi4166 pkd2+/- were compared to sibling pkd2+/+ (males). Total kidney volume and texture were quantified from MRI in vivo (16mo, n=3). Collagen density was quantified from picrosirius red (PSR) stained sections using polarized light microscopy and ImageJ for color thresholding (19m, n=3). Integrity of the collagen triple helix was assessed in kidney frozen sections labeled with collagen hybridizing peptide in zebrafish (18m, n=4) and mouse Pkd1RC/RC (10m).

Results

Kidney volumes were not different; however, texture analysis showed pkd2+/- kidney was more heterogeneous. This was not explained by cysts, as none were visible by H&E staining, nor were tubule diameters different. PSA staining showed significantly more dense collagen, and collagen hybridizing peptide labeling showed more denatured collagen in pkd2+/- zebrafish kidney. Preliminary data from Pkd1RC/RC mice show similar patterns of collagen density and denaturation.

Conclusion

To our knowledge, this is the first report of any phenotype in pkd2+/- zebrafish (adult or embryo). The presence of a dominant phenotype and a collagen defect suggests conservation of disease etiology. A collagen defect in the absence of cysts indicates independence of collagen changes from cyst formation, suggesting collagen changes may be a primary defect in PKD pathophysiology.

Increased collagen density in kidney of pkd2 mutant zebrafish visualized by staining with picrosirius red and imaging using polarized light (left) quantified using image thresholding in ImageJ (right). Pixels are binned by color indicating density as shown.

Funding

  • NIDDK Support