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

Schenk, Laura K. and Buchholz, Bjoern and Henke, Sebastian F. and Michgehl, Ulf and Daniel, Christoph and Amann, Kerstin and Kunzelmann, Karl and Pavenstaedt, Hermann (2018) Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 315 (6). F1777-F1786. ISSN 1931-857X, 1522-1466

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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 endowment. Loss of TMEM16A resulted in reduced nephron number and, subsequently, albuminuria and tubular damage.

Item Type: Article
Uncontrolled Keywords: CHLORIDE CHANNELS; PROLIFERATION; HYPOXIA; GUDMAP; MICE; FORM; albuminuria; Ano1; kidney; nephron number; TMEM16A
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 Oct 2019 08:42
Last Modified: 04 Oct 2019 08:42
URI: https://pred.uni-regensburg.de/id/eprint/13410

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