Zebrafish Kidney Disease Models

Zebrafish Kidney Disease Models

Within the realm of kidney biology, zebrafish has been established as an outstanding model to study disease afflictions that alter nephron development and physiology. A series of traits makes zebrafish amenable for organ development and disease studies in the embryo. For instance, zebrafish development occurs ex utero, and the embryos are optically clear, allowing researchers to readily observe processes in real-time within the whole-animal context. Detailed molecular characterization of renal anatomy in the zebrafish showed the overall conservation of nephron segment pattern and cellular composition in both embryonic and adult kidney structures compared with those of other vertebrates. Large-scale mutagenesis screens have identified multiple mutants affecting kidney development enabling the exploration of genetic and molecular mechanisms underlying pronephros development and function. Besides, reverse genetics approaches allow researchers to specifically alter orthologous genetic elements potentially associated with human disease. So far, major fields of research where such zebrafish models are being employed include glomerular and cystic renal disorders.

The zebrafish pronephros shares genetic conservation with the human nephron.

Figure 1. The zebrafish pronephros shares genetic conservation with the human nephron. (Poureetezadi S J, et al. 2016)

Creative Biogene, a zebrafish preclinical contract research organization, offers a suite of zebrafish kidney disease models that be used to understand the molecular and cellular basis of the disease, assess the functional role of human genetic variations, and screen potential compounds for kidney disease therapy. Usually, there are two main approaches for generating kidney disease modeling in the zebrafish: forward genetics and reverse genetics.

Table 1. Attributes of key methods used to generate the zebrafish disease model. (Elmonem M A, et al. 2018)

Forward GeneticsReverse Genetics
ENU MutagenesisRetroviral InsertionMOCRISPR-Cas9
Genetic targetGenomic DNAGenomic DNAmRNAGenomic DNA
Mutation siteRandomRandomNo DNA mutationsspecific DNA sequence
Mutational effectMainly deficiencyMainly deficiencyDeficiencyDeficiency/Gain
Stage of inducing mutagenesisAdult malesBlastulae1-4 cell stage1 cell stage
Difficulty of confirming the mutant genotypeDifficultLess difficultEasyEasy
Efficiency of mutagenesisMediumLowHighHigh
Mutant modelPermanentPermanentTransientPermanent
Time, effort and resources++++++++++
Off-target effects++++++

ENU, N-ethyl-N-nitrosourea; MO, morpholino antisense oligonucleotides.

To date, Creative Biogene has developed a variety of zebrafish kidney disease model, including but not limited to:

  • Glomerular disease models
  • Acute kidney injury (AKI) models
  • Polycystic kidney disease and other ciliopathies models

Besides, for the larval zebrafish to be a valid model to study renal disease and potential new therapies, the availability of methods for the assessment of renal function in this organism is necessary. Thus, we also developed a new panel of methodologies to accurately evaluate different aspects of renal function in the larval zebrafish.

  • Evaluation of Zebrafish Survival, Development, and Morphology
  • Evaluation of Glomerular Function
  • Evaluation of Tubular Function
  • Evaluation of Renal Cysts

With extensive experience in zebrafish research, our scientists can help you choose the right model and experimental design to achieve your research and development goals.

References

  • Elmonem M A, et al. Genetic renal diseases: the emerging role of zebrafish models. Cells, 2018, 7(9): 130.
  • Gehrig J, et al. Zebrafish as a model for drug screening in genetic kidney diseases. Frontiers in pediatrics, 2018, 6: 183.
  • Outtandy P, et al. Zebrafish as a model for kidney function and disease. Pediatric Nephrology, 2019, 34(5): 751-762.
  • Poureetezadi S J, Wingert R A. Little fish, big catch: zebrafish as a model for kidney disease. Kidney international, 2016, 89(6): 1204-1210.
  • Morales E E, Wingert R A. Zebrafish as a model of kidney disease. Kidney Development and Disease. Springer, Cham, 2017: 55-75.

For research use only. Not intended for any clinical use.

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