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

Schenk LK, Buchholz B, Henke SF, Michgehl U, Daniel C, Amann KU, Kunzelmann K, Pavenstaedt H (2018)

Publication Type: Journal article

Publication year: 2018

Journal

American Journal of Physiology-Renal Physiology American Physiological Society

Book Volume: 315

Pages Range: F1777-F1786

Journal Issue: 6

DOI: 10.1152/ajprenal.00638.2017

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

Authors with CRIS profile

Björn Buchholz Department of Medicine 4 – Nephrology and Hypertension Christoph Daniel Department of Nephropathology Kerstin Ute Amann Department of Nephropathology

Involved external institutions

Universitätsklinikum Münster DE Germany (DE) Universität Regensburg DE Germany (DE)

How to cite

APA:

Schenk, L.K., Buchholz, B., Henke, S.F., Michgehl, U., Daniel, C., Amann, K.U.,... Pavenstaedt, H. (2018). Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria. American Journal of Physiology-Renal Physiology, 315(6), F1777-F1786. https://doi.org/10.1152/ajprenal.00638.2017

MLA:

Schenk, Laura K., et al. "Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria." American Journal of Physiology-Renal Physiology 315.6 (2018): F1777-F1786.

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