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.

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 Genetics		Reverse Genetics
	ENU Mutagenesis	Retroviral Insertion	MO	CRISPR-Cas9
Genetic target	Genomic DNA	Genomic DNA	mRNA	Genomic DNA
Mutation site	Random	Random	No DNA mutations	specific DNA sequence
Mutational effect	Mainly deficiency	Mainly deficiency	Deficiency	Deficiency/Gain
Stage of inducing mutagenesis	Adult males	Blastulae	1-4 cell stage	1 cell stage
Difficulty of confirming the mutant genotype	Difficult	Less difficult	Easy	Easy
Efficiency of mutagenesis	Medium	Low	High	High
Mutant model	Permanent	Permanent	Transient	Permanent
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.