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Kidney Week

Abstract: TH-PO692

Hearing Impairment, a Novel Functional Readout, in Pkd2 Mutant Zebrafish

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic


  • Sussman, Caroline R., Mayo Clinic, Rochester, Minnesota, United States
  • Pearson, Elisabeth, Mayo Clinic, Rochester, Minnesota, United States
  • Andrews, Leah, Mayo Clinic, Rochester, Minnesota, United States
  • Johnson, Kaitlyn Mary, Mayo Clinic, Rochester, Minnesota, United States
  • Koleilat, Alaa, Mayo Clinic, Rochester, Minnesota, United States
  • Ekker, Stephen C., Mayo Clinic, Rochester, Minnesota, United States
  • Schimmenti, Lisa A., Mayo Clinic, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic, Rochester, Minnesota, United States

Zebrafish have been a valuable model for studies of PKD, with conservation of phenotypes and signaling pathways. Phenotypic readouts have consisted mainly of pronephric cysts and body curvature. The only method for assessing kidney function in embryos is dye clearance, which is affected by many factors and, therefore, is not a reliable indicator. Hair cells of the ear and zebrafish lateral line share many features in common with renal epithelial cells and are responsible for hearing. We have identified hearing assays as a novel approach for assessing pkd2 function.


We assayed hearing using a standard acoustic startle response (ASR) in 6-7 day old zebrafish. 100 or 400 Hz stimuli were delivered using MATLAB, and responses were recorded using a video camera. Startle responses consisted of a sudden change in swimming velocity or direction in response to the tone and were scored as 1 or 0 for presence or absence, respectively.


The ASR assay was validated using neomycin to ablate lateral line hair cells by established methods. After one hour in neomycin no hair cells were visible using yo-pro-1 or daspei vital dyes and the frequency of response to a 400 Hz tone was reduced 50% compared to untreated sibling controls (0.5±0.2 vs 0.24±0.2, p<0.04, n=24 fish/group from 3 clutches). The response of hi4166 pkd2-/- zebrafish to a 400 Hz tone was reduced 35% compared to wild-type sibling controls (0.50±0.2 vs. 0.17±0.2, p<0.03, n=56 fish/group from 7 clutches). This population of fish also responded 30% less frequently to a 100 Hz tone (0.83±0.1 vs 0.24±0.1, p<0.0001). Our ASR assay was additionally validated using a novel transposon mutant line, spinner. This line develops ventral body curvature, pronephric cysts, and fails to develop hair cell kinocilia analogous to the central cilium, as determined by acetylated alpha tubulin labeling. Spinner mutants show profound hearing loss at both 400 and 100 Hz (0.88±0 vs 0.04±0 and 0.93±0.1 vs 0.12±0.1, p<0.001, n=16-24 fish/group from 2-3 clutches).


These data show that the established hi4166 pkd2 mutant zebrafish line have hearing loss, suggesting hearing can be used as an alternative to dye clearing assays for pkd2 function in zebrafish. They further suggest the relevance of hair cells as a model for studies of PKD.


  • NIDDK Support