ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-PO500

Muc1 Deficiency Causes Urinary Acidification Defects in Mice

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic


  • Al-bataineh, Mohammad M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Ray, Evan C., UPMC, Pittsburgh, Pennsylvania, United States
  • Kinlough, Carol L., Department of Medicine University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Hughey, Rebecca P., Dept Medicine-Renal Electrolyte Division, Pittsburgh, Pennsylvania, United States
  • Kleyman, Thomas R., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Mucin 1 (human MUC1, mouse Muc1) is expressed on the apical surface of most epithelial cells, including the thick ascending limb (TAL) and distal nephron segments. Proximal tubular expression of Muc1 is induced in ischemia-reperfusion injury, where it stabilizes HIF-1a and b-catenin and plays a protective role. A frame-shift mutation in MUC1 causes autosomal dominant tubulointerstitial kidney disease. However, there is limited information regarding its functional role in normal kidney. Muc1 knockout mice have no clear phenotype in the absence of stressors (e.g. bacterial infection). The TRPV5 Ca2+ channel was reported to be stabilized on the cell surface by galectin-dependent cross-linking to MUC1, providing a novel mechanism for regulation of this ion channel. We observed robust Muc1 apical and sub-apical staining in type A and type B intercalated cells (ICs). In Type A ICs, Muc1 co-localizes with the vacuolar H+ ATPase (V-ATPase), a protein complex that mediates apical ATP-driven H+ secretion. V-ATPase subcellular localization regulates H+ secretion, while defects in V-ATPase function can cause renal tubular acidosis. As Muc1 and the V-ATPase are highly expressed in ICs, we tested the hypothesis that Muc1 regulates V-ATPase expression and function.


Muc1 KO (Muc1-/-), Muc1 heterozygous (Muc1+/-) and control mice were given 2.5% sucrose with or without 0.28 M NH4Cl in drinking water for 7 days. Plasma electrolytes, urine pH and NH4+ were measured. Kidneys were processed for immunoblotting and confocal immunofluorescence (IF) microscopy.


IF staining of fixed mouse kidney slices revealed that Muc1 co-localizes with luminal V-ATPase in ICs. Moreover, V-ATPase moved from the cytosol to the apical surface when WT mice were subjected to an acid load. In contrast, V-ATPase remained cytosolic in Muc1-/- mice. In response to acid-loading, both Muc1-/- and Muc1+/- mice exhibited impaired urinary acidification while only Muc1 KO mice exhibited greater metabolic acidosis. The IC-specific a4-subunit of V-ATPase co-immunoprecipitated with Muc1 in extracts of mouse kidney, suggesting that they are components of a protein complex.


These results suggest that Muc1 interacts with the V-ATPase and influences its cell surface localization in type A ICs, and is necessary for a normal renal response to an acid load.


  • NIDDK Support