Zebrafish Kidney Ciliopathy Models

Cilia are highly conserved organelles that are an integral part of virtually all vertebrate cells, and cilia dysfunction can manifest in a range of features that include retinal degeneration, kidney disease, and brain abnormalities. Ciliopathies are a group of rare human genetic disorders that are caused by defects in primary cilia. Typical ciliopathies include Bardet-Biedl syndrome (BBS), nephropathy (NPHP), Jeune, Joubert, orofacial indication (OFD1), and Meckel (MKS) syndrome. All cilia have common features of renal disease, often including tubular cysts.

Over the past decade, the zebrafish has proven to be an excellent vertebrate model for genetic analysis and imaging of cilia-related processes. The developing zebrafish larva is mostly transparent and has differentiated cilia during early stages of embryogenesis. Therefore, immunostaining for ciliary proteins combined with confocal microscopy allows for easy examination of the morphology and movement of cilia during organ development in zebrafish. Furthermore, zebrafish are developing as an effective model for studying cystic kidney disease in humans. Zebrafish pronephros develop at 2 days post fertilization (dpf) and are easily screened for the presence of cysts at 3 dpf. These cysts often impair renal function, causing body edema at 4 dpf. Additionally, ex vivo development allows the addition of therapeutic compounds directly to the water in which the eggs are hatched.

Fig.1 Metformin inhibits pronephric cyst formation in pkd2 morphants.

Our Zebrafish Kidney Ciliopathy Models

Creative Biogene uses TALENs and the CRISPR/Cas9 nuclease system for targeted genomic mutagenesis to generate a variety of zebrafish kidney models. For various ciliopathies, we provide a variety of zebrafish mutants, including AHI1, ARL13B, ARL6, ARMC9, CC2D2A, Exoc5, IFT122, NBCe1, POC1B, and TMEM67, etc. They have a renal phenotype and can be used to study the pathogenesis of renal ciliopathies and develop potential treatments for ciliopathies. We aim to create fish models for most known human ciliopathies, screen them for renal phenotypes, and then help you screen for compounds that can prevent cyst formation and potentially restore function.

Table 1 Zebrafish Kidney Ciliopathy Models

Cilia Gene	Kidney Phenotype	Disease
AHI1 mutant	Kidney cysts	Joubert syndrome
ARL13B mutant	Kidney cysts	Joubert syndrome
ARL6 mutant	Polydactylyrenal malformations	Bardet-Biedl syndrome
ARMC9 mutant	Fibrocystic kidney disease	Joubert syndrome
CC2D2A mutant	Pronephric cyst	Meckel-Gruber syndrome
Exoc5 Mutants	Glomerular expansion left-right patterning defects	PKD
IFT122 mutation	Cystic kidney	RP
NBCe1 mutation	Pronephric ducts defect	renal tubular acidosis
POC1B Mutation	Cystic kidney	Joubert syndrome, polycystic kidney disease, Leber's congenital amaurosis
TMEM67 mutation	Bilateral pronephric cysts	Meckel-Gruber syndrome

Advantages

High-throughput gene and drug screening
Rapidly perform reverse and forward genetic screening
Easily examine the morphology and movement of cilia during zebrafish organ development
Rapid Morphological Scoring

References

Chang MY, et al. Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency. Sci Rep. 2017, 7(1):7161.
Shi Y, et al. Zebrafish as models to study ciliopathies of the eye and kidney. Clin Nephrol Res. 2017, 1(1):6-9.
Tobin JL, Beales PL. Restoration of renal function in zebrafish models of ciliopathies. Pediatr Nephrol. 2008, 23(11):2095-2099.

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

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