Shroom3 is required for nephron development (540.9)

Reduced nephron number is linked with chronic kidney disease and adult onset hypertension. Defects in the formation of nephrons are a major factor in determining nephron number. Multiple genome wide association studies have strongly linked SHROOM3 with altered kidney function and chronic kidney disease. Yet, the role of SHROOM3 in kidney function and nephron formation is not known. We utilized Shroom3-/- and Shroom3+/- mutant mice containing a gene trap β-galactosidase reporter to analyze Shroom3 expression. LacZ expression localized shroom3 to cap mesenchyme and podocytes throughout kidney development. LacZ expression was only observed in the collecting ducts after E15.5. LacZ expression was maintained in the podocyte and collecting ducts in mature kidneys. Immunohistochemistry using a Shroom3 antibody confirmed the dynamic spatial and temporal expression pattern. Histological analysis of kidneys from Shroom3-/- mice demonstrated numerous condensed and cystic glomeruli at E13.5. Abnormal glomeruli demons...