Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria

American Journal of Physiology. Renal Physiology
Laura K SchenkHermann Pavenstädt

Abstract

TMEM16A is a transmembrane protein from a conserved family of calcium-activated proteins that is highly expressed in the kidney. TMEM16A confers calcium-activated chloride channel activity, which is of importance for various cellular functions in secretory epithelia and involved in secretion-dependent renal cyst growth. However, its specific function in renal physiology has remained elusive so far. Therefore, we generated conditional nephron-specific TMEM16A-knockout mice and found that these animals suffered from albuminuria. Kidney histology demonstrated an intact corticomedullary differentiation and absence of cysts. Electron microscopy showed a normal slit diaphragm. However, the total number of glomeruli and total nephron count was decreased in TMEM16A-knockout animals. At the same time, glomerular diameter was increased, presumably as a result of the hyperfiltration in the remaining glomeruli. TUNEL and PCNA stainings showed increased cell death and increased proliferation. Proximal tubular cilia were intact in young animals, but the number of properly ciliated cells was decreased in older, albuminuric animals. Taken together, our data suggest that TMEM16A may be involved in ureteric bud branching and proper nephron endow...Continue Reading

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Citations

Feb 15, 2019·Frontiers in Pharmacology·Karl KunzelmannRoberta Benedetto
Mar 22, 2019·Cancers·Karl KunzelmannRainer Schreiber
Aug 30, 2020·Nature Communications·Ines CabritaBjörn Buchholz
Jun 4, 2020·Journal of Medical Genetics·Julien H ParkThorsten Marquardt

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Methods Mentioned

BETA
electrophoresis
PCR
electrophoreses
electron microscopy

Software Mentioned

GraphPad Prism
ImageJ

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