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

Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria. Am J Physiol Renal Physiol. 2018 Aug 29;: Authors: Schenk LK, Buchholz B, Henke SF, Michgehl U, Daniel C, Amann K, Kunzelmann K, Pavenstadt HJ Abstract TMEM16A is a transmembrane protein from a conserved family of calcium activated proteins, which 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 suggests that TMEM16A may be involved in ureteric bud b...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research