Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

Recently, recessive mutations of MAGI2 were identified as a cause of steroid-resistant nephrotic syndrome (SRNS) in humans and mice. To further delineate the pathogenesis of MAGI2 loss of function, we generated stable knockout lines for the two zebrafish orthologues magi2a and magi2b by CRISPR/Cas9. We also developed a novel assay for the direct detection of proteinuria in zebrafish independent of transgenic background. Whereas knockout of magi2b did not yield a nephrotic syndrome phenotype, magi2a-/- larvae developed ascites, periorbital edema, and proteinuria, as indicated by increased excretion of low molecular weight protein.

Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Tilman Jobst-Schwan, Charlotte A. Hoogstraten, Caroline M. Kolvenbach, Johanna Magdalena Schmidt, Amy Kolb, Kaitlyn Eddy, Ronen Schneider, Shazia Ashraf, Eugen Widmeier, Amar J. Majmundar, Friedhelm Hildebrandt Tags: Basic Research Source Type: research