title: Deletion of the chloride transporter slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion.
abstract: SLC26A7 (human)/Slc26a7 (mouse) is a recently identified chloride-base exchanger and/or chloride transporter that is expressed on the basolateral membrane of acid-secreting cells in the renal outer medullary collecting duct (OMCD) and in gastric parietal cells. Here, we show that mice with genetic deletion of Slc26a7 expression develop distal renal tubular acidosis, as manifested by metabolic acidosis and alkaline urine pH. In the kidney, basolateral Cl(-)/HCO3(-) exchange activity in acid-secreting intercalated cells in the OMCD was significantly decreased in hypertonic medium (a normal milieu for the medulla) but was reduced only mildly in isotonic medium. Changing from a hypertonic to isotonic medium (relative hypotonicity) decreased the membrane abundance of Slc26a7 in kidney cells in vivo and in vitro. In the stomach, stimulated acid secretion was significantly impaired in isolated gastric mucosa and in the intact organ. We propose that SLC26A7 dysfunction should be investigated as a potential cause of unexplained distal renal tubular acidosis or decreased gastric acid secretion in humans.
authors.affiliation: Research Services, Veterans Affairs Medical Center, Cincinnati, Ohio 45220, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Penghong
authors.initials: P
authors.lastname: Song
authors.forename: Suguru
authors.initials: S
authors.lastname: Nakamura
authors.forename: Marian
authors.initials: M
authors.lastname: Miller
authors.forename: Sharon
authors.initials: S
authors.lastname: Barone
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.forename: Janina
authors.initials: J
authors.lastname: Bonhagen
authors.forename: Lois J
authors.initials: LJ
authors.lastname: Arend
authors.forename: Hassane
authors.initials: H
authors.lastname: Amlal
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.forename: Manoocher
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D027963:Chloride-Bicarbonate Antiporters; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007679:Kidney Medulla / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D000076988:Sulfate Transporters
chemical_list: D027963:Chloride-Bicarbonate Antiporters; C486743:Slc26a7 protein, mouse; D000076988:Sulfate Transporters