1. Université Libre de Bruxelles (U.L.B.), Institut de Biologie et de Médecine Moléculaires, Laboratoires de Biologie du Développement et de Physiologie Moléculaire de la Cellule, Rue Professeurs Jeener et Brachet, 12, B-6041 Gosselies, Belgium
2. Université catholique de Louvain (U.C.L.), Division of Nephrology, Avenue Hippocrate, 54, B-1200 Brussels, Belgium
3. Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland
4. INSERM UMRS 872; Université Pierre et Marie Curie; Université Paris-Descartes; F-75006 Paris, France
5. These authors contributed equally to this work.
6. Present address: Delphi Genetics, B-6041 Gosselies, Belgium.

Correspondence to: Anna Maria Marini¹ Correspondence and requests for materials should be addressed to A.M.M. (Email: ammarini@dbm.ulb.ac.be).

Abstract

The kidney has an important role in the regulation of acid–base homeostasis. Renal ammonium production and excretion are essential for net acid excretion under basal conditions and during metabolic acidosis. Ammonium is secreted into the urine by the collecting duct, a distal nephron segment where ammonium transport is believed to occur by non-ionic NH₃ diffusion coupled to H⁺ secretion. Here we show that this process is largely dependent on the Rhesus factor Rhcg. Mice lacking Rhcg have abnormal urinary acidification due to impaired ammonium excretion on acid loading—a feature of distal renal tubular acidosis. In vitro microperfused collecting ducts of Rhcg^-/- acid-loaded mice show reduced apical permeability to NH₃ and impaired transepithelial NH₃ transport. Furthermore, Rhcg is localized in epididymal epithelial cells and is required for normal fertility and epididymal fluid pH. We anticipate a critical role for Rhcg in ammonium handling and pH homeostasis both in the kidney and the male reproductive tract.

1. Université Libre de Bruxelles (U.L.B.), Institut de Biologie et de Médecine Moléculaires, Laboratoires de Biologie du Développement et de Physiologie Moléculaire de la Cellule, Rue Professeurs Jeener et Brachet, 12, B-6041 Gosselies, Belgium
2. Université catholique de Louvain (U.C.L.), Division of Nephrology, Avenue Hippocrate, 54, B-1200 Brussels, Belgium
3. Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland
4. INSERM UMRS 872; Université Pierre et Marie Curie; Université Paris-Descartes; F-75006 Paris, France
5. These authors contributed equally to this work.
6. Present address: Delphi Genetics, B-6041 Gosselies, Belgium.

Correspondence to: Anna Maria Marini¹ Correspondence and requests for materials should be addressed to A.M.M. (Email: ammarini@dbm.ulb.ac.be).

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