Zebrafish PKD-Targeted Services

The Model Systems Core offers zebrafish PKD-targeted services to PKD researchers both at Mayo Clinic and at other institutions.

These services are supported and complemented by the Zebrafish Facility at Mayo Clinic, which provides animal housing and extensive technical expertise.

The zebrafish is the premier nonmammalian vertebrate model organism that has a kidney, and it is well established as a model system for the study of polycystic kidney disease and other ciliopathies.

For PKD research, the zebrafish model can be used to understand the molecular and cellular basis of the disease, assess the functional role of human genetic variations, and screen for small-molecule suppressors in PKD zebrafish embryonic disease models.

Services

The Model Systems Core offers several zebrafish PKD-targeted services:

  • Small-molecule screening for cystic phenotype effects. A screen for small-molecule suppressors of a PKD zebrafish embryonic disease model demonstrated the viability of using zebrafish to explore chemical genetics questions. In addition, one major emphasis in PKD is the potential use of combination treatment approaches, so the zebrafish offers an opportunity to explore new small molecules and combinations of known drugs for preclinical efficacy testing. [1]
  • Evaluation of pathways relevant to PKD, including, for example, microinjection of mRNAs or antisense morpholino oligonucleotides into embryos. The zebrafish embryo enables rapid in vivo testing of specific hypotheses related to PKD disease formation and progression. [2]
  • Custom TALEN synthesis for targeted gene mutations. We offer assistance with TALEN design and synthesis and provide training on mutation screening and line development. [3]
  • Human sequence variation functional testing. Zebrafish can be used to discern functional differences in human sequence variation of candidate PKD loci. The Zebrafish Facility provides expertise to run comparable in vivo functional tests for human sequence variants identified in the Mayo Clinic Pirnie Translational Polycystic Kidney Disease Center. [4, 5]
  • Novel quantitative phenotyping, including MRI of adult zebrafish kidney allowing 3D reconstruction and texture analysis. [6]
  • Targeted training on current zebrafish technologies.

Related publications

  1. Zhu P, Sieben CJ, Xu X, Harris PC, Lin X. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Human Molecular Genetics. 2017; doi:10.1093/hmg/ddw376.
  2. Sussman CR, Ward CJ, Leightner AC, Smith JL, Agarwal R, Harris PC, Torres VE. Phosphodiesterase 1A modulates cystogenesis in zebrafish. Journal of the American Society of Nephrology. 2014; doi:10.1681/ASN.2013040421.
  3. Zhu P, J Sieben CJ, Xu X, Harris PC, Lin X. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Human Molecular Genetics. 2017; doi:10.1093/hmg/ddw376.
  4. WareJoncas Z, Campbell JM, Martínez-Gálvez G, Gendron WAC, Barry MA, Harris PC, Sussman CR, Ekker SC. Precision gene editing technology and applications in nephrology. Nature Reviews Nephrology. 2018; doi:10.1038/s41581-018-0047-x.
  5. Ata H, Ekstrom TL, Martínez-Gálvez G, Mann CM, Dvornikov AV, Schaefbauer KJ, Ma AC, Dobbs D, Clark KJ, Ekker SC. Robust activation of microhomology-mediated end joining for precision gene editing applications. PLOS Genetics. 2018; doi:10.1371/journal.pgen.1007652.
  6. Kline TL, Sussman CR, Irazabal MV, Mishra PK, Pearson EA, Torres VE, Macura SI. Three-dimensional NMR microscopy of zebrafish specimens. NMR in Biomedicine. 2019; doi:10.1002/nbm.4031.

Contact

Email us for more information about zebrafish PKD services and available lines for distribution.