Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis

Although focal and segmental glomerulosclerosis (FSGS) has been in the scientific focus for many years, it is still a massive burden for patients with no causal therapeutic option. In FSGS, podocytes are injured, parietal epithelial cells (PECs) are activated and engage in the formation of cellular lesions leading to progressive glomerular scarring. Herein we show that podocyte-depleted zebrafish larvae develop acute proteinuria, severe foot process effacement and activate PECs which create cellular lesions and deposit extracellular matrix on the glomerular tuft. We therefore propose that this model shows features of human FSGS and show its applicability for a high-throughput drug screening assay.