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The glomerulus and nephrotic syndrome

The kidney glomerulus is a selective blood filter, preserving cells and protein in the vascular space and filtering plasma. Nephrotic syndrome occurs when protein leaks into the blood filtrate due to structural defects in the kidney glomerulus. We modeled human nephropathy gene deficiencies (nephrin, podocin) in zebrafish and developed a new assay for glomerular function. Based on this assay we discovered new genes and pathways causing nephrotic syndrome. We showed that mutation in the FERM domain protein mosaic eyes, a component of the Crumbs apical polarity pathway, caused podocyte defects and proteinuria, implicating the apical polarity pathway in nephrotic syndrome. Our functional assay in zebrafish also enabled the identification of Phospholipase C epsilon as a novel human nephrotic syndrome gene. Our current work is examining podocyte cell signal transduction and calcium mobilizing stimuli that drive podocyte-capillary interactions.

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