A zebrafish model of congenital nephrotic syndrome of the Finnish type

A zebrafish model of congenital nephrotic syndrome of the Finnish type

Blog Article

Nephrotic syndrome (NS) is a sukin body lotion woolworths disease characterized by proteinuria and subsequent hypoalbuminemia, hyperlipidemia and edema due to the defective renal glomerular filtration barrier (GFB).Mutations of NPHS1, encoding NEPHRIN, a podocyte protein essential for normal GFB, cause congenital nephrotic syndrome (CNS) of the Finnish type (CNF), which accounts for about 50% of CNS cases.We generated zebrafish nphs1 mutants by using CRISPR/Cas9.

These mutants completely lack nephrin proteins in podocytes and develop progressive peri-orbital and whole-body edema after 5 days post fertilization.Ultra-structurally, loss of nephrin results in absence of slit-diaphragms and progressive foot process effacement in zebrafish pronephric glomeruli, similar to the pathological sukrensi.com changes in human CNF patients.Interestingly, some nphs1 mutants are viable to adulthood despite ultra-structural defects in renal glomeruli.

Using a reporter line Tg (l-fabp:VDBP-GFP) expressing GFP-tagged vitamin-D-binding protein in the blood plasma, we observed a reduction of intravascular GFP fluorescence in the nphs1 mutants, a hypoalbuminemia-like phenotype.In addition, we detected excretion of GFP by the nphs1 mutants, reminiscent of proteinuria.Therefore, we have demonstrated that the nphs1 mutant zebrafish recapitulate the human NS phenotypes and provide a novel and relevant animal model useful for screening therapeutical agents for this disease.