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WDR72 Is Required for Urinary Acidification and Normal H+-ATPase Activity in Intercalated Cells in Mice
Hannah Auwerx1, Moana Busch-Dohr1, Xiaoxu Li2
1Institute of Physiology, University of Zurich, Zurich, Switzerland.
Acta Physiologica (Oxford, England)
|February 4, 2026
Summary
WDR72 protein is crucial for kidney acid excretion, particularly in female mice. Its dysfunction leads to altered acid-base balance and impacts the H+-ATPase in intercalated cells.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- WDR72 variants are associated with distal renal tubular acidosis (dRTA), nephrocalcinosis, and amelogenesis imperfecta.
- The kidney exhibits high WDR72 expression, but its specific localization and function in renal acid-base homeostasis are not well understood.
- WDR72, a WD40 repeat protein, is implicated in vesicular trafficking, suggesting a potential role in cellular transport mechanisms.
Purpose of the Study:
- To investigate the expression pattern of WDR72 in the kidney.
- To elucidate the role of WDR72 in renal acid-base homeostasis and its connection to the H+-ATPase.
- To explore potential sex-specific functions of WDR72 in renal physiology.
Main Methods:
- Analysis of single-cell transcriptome data from human and murine kidneys to determine WDR72 expression.
- Characterization of Wdr72 knockout (Wdr72-/-) mice (female and male) to assess renal function.
- Assessment of Wdr72 mRNA and protein localization, urinary acid excretion capacity, and H+-ATPase expression and activity.
Main Results:
- WDR72 is highly expressed in intercalated cells and other nephron segments, predominantly at the apical membrane of type A-intercalated cells.
- Wdr72-/- mice showed alkaline urine; female knockout mice developed metabolic acidosis upon dietary acid loading.
- Dysregulated expression of H+-ATPase subunits was observed in Wdr72-/- kidneys, correlating with reduced H+-ATPase activity.
Conclusions:
- WDR72 is identified as a key regulator of urinary acidification mediated by type A-intercalated cells, influencing H+-ATPase activity.
- The study reveals a novel mechanism for sex differences in renal acid handling, highlighted by the sex-specific metabolic phenotype in Wdr72-/- mice.
- These findings underscore the importance of WDR72 in maintaining kidney acid-base balance and suggest its dysfunction contributes to renal tubular acidosis.
Keywords:
WD40 repeat domain proteinacid–base homeostasisdistal renal tubular acidosisintercalated cellssex differenceMore Related Videos
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