Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis
- Hansen, K.U.I., Siegerist, F., Daniel, S., Schindler, M., Iervolino, A., Blumenthal, A., Daniel, C., Amann, K., Zhou, W., Endlich, K., Endlich, N.
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34(12): 15961-15974 (Journal)
- Registered Authors
- Zhou, Weibin
- FSGS, glomerulus, podocyte injury, zebrafish model organism
- MeSH Terms
- Animals, Genetically Modified
- Disease Models, Animal
- Epithelial Cells/pathology
- Glomerulosclerosis, Focal Segmental/pathology*
- Kidney Glomerulus/pathology*
- Nephrotic Syndrome/pathology
- 33070374 Full text @ FASEB J.
Hansen, K.U.I., Siegerist, F., Daniel, S., Schindler, M., Iervolino, A., Blumenthal, A., Daniel, C., Amann, K., Zhou, W., Endlich, K., Endlich, N. (2020) Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 34(12):15961-15974.
Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end-stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies. Here, we present an FSGS-like model in zebrafish larvae, an eligible vertebrate model for kidney research. In a transgenic zebrafish strain, podocytes were depleted, and the glomerular response was investigated by histological and morphometrical analysis combined with immunofluorescence staining and ultrastructural analysis by transmission electron microscopy. By intravenous injection of fluorescent high-molecular weight dextran, we confirmed leakage of the size selective filtration barrier. Additionally, we observed severe podocyte foot process effacement of remaining podocytes, activation of proximal tubule-like parietal epithelial cells identified by ultrastructural cytomorphology, and expression of proximal tubule markers. These activated cells deposited extracellular matrix on the glomerular tuft which are all hallmarks of FSGS. Our findings indicate that glomerular response to podocyte depletion in larval zebrafish resembles human FSGS in several important characteristics. Therefore, this model will help to investigate the disease development and the effects of potential drugs in a living organism.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes