Zebrafish Polycystic Kidney Disease Models

Polycystic kidney disease (PKD), one of the most common causes of end-stage renal disease, is an inherited disorder that produces abnormal cell proliferation, fluid accumulation in massive cysts, extracellular matrix remodeling, inflammation, and Kidney fibrosis. The molecular mechanisms responsible for cyst formation in PKD remain unclear, but many genes are thought to be involved. In PKD progression, key roles of signaling pathways including MAPK, mTOR, and PPAR-γ have been discovered in animal models. Therefore, experimental animal models are essential to study the molecular mechanisms of PKD pathogenesis and progression, as well as potential therapeutic approaches.

Zebrafish embryos have been widely used as a model to study kidney development and polycystic kidney disease. Using zebrafish as an animal model has many advantages: the feasibility of studying genetic interactions, the ability to use antisense morpholinos for protein knockouts, the opportunity to rapidly assay large numbers of embryos, and the ease of viewing larval organ phenotypes in living organisms with mammalian rearing Compared to the kidney (the third and last kidney to develop in mammals), the structure of the zebrafish prenephros is relatively simple. Zebrafish have only two nephrons, and each zebrafish nephron contains all the major components in mouse and human glomeruli and tubules, as well as similar specialized kidney cell types.

Fig.1 PKD in mammals and zebrafish.

Our Zebrafish Polycystic Kidney Disease Models

Creative Biogene can screen small molecules for cystic phenotypic effects in zebrafish models of polycystic kidney disease. Furthermore, a major focus of PKD is the potential use of combination therapeutic approaches, and our zebrafish model could provide an opportunity to explore new small molecule and known drug combinations for preclinical efficacy testing. Our model can also be used to assess PKD-related pathways including, for example, microinjection of mRNA or antisense morpholino oligonucleotides into embryos. Our zebrafish embryo models enable rapid in vivo testing of specific hypotheses related to PKD disease development and progression.

Additionally, we can use zebrafish to study the impact of mutations in target genes that play a role in kidney physiology, and use this knowledge to help researchers learn more about the effects of genes in humans. By targeting germline mutations, we can also assess the impact of specific mutations to assess the pathogenicity of genetic variants found in patients with kidney disease. Our zebrafish model can also be used to study basic kidney physiology. Overall, we are committed to providing you with useful models for studying kidney function and disease.

Advantages

• Rapid analysis of phenotypes of interest
• High-throughput screening of compounds
• Numerous genes tested for possible kidney cyst formation
• Real-time observation of the disease process

References

1. Marra AN, Li Y, Wingert RA. Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development. Genesis. 2016, 54(9):457-69.
2. Huang L, et al. A possible zebrafish model of polycystic kidney disease: knockdown of wnt5a causes cysts in zebrafish kidneys. J Vis Exp. 2014, (94):52156.
3. Ren Z, et al. Novel zebrafish polycystic kidney disease models reveal functions of the Hippo pathway in renal cystogenesis. Dis Model Mech. 2021, 14(11):dmm049027.
4. Outtandy P, et al. Zebrafish as a model for kidney function and disease. Pediatr Nephrol. 2019, 34(5):751-762.

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