Deletion of the chloride transporter slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion.
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.
Xu
Jie
J
Research Services, Veterans Affairs Medical Center, Cincinnati, Ohio 45220, USA.
Song
Penghong
P
Nakamura
Suguru
S
Miller
Marian
M
Barone
Sharon
S
Alper
Seth L
SL
Riederer
Brigitte
B
Bonhagen
Janina
J
Arend
Lois J
LJ
Amlal
Hassane
H
Seidler
Ursula
U
Soleimani
Manoocher
M
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
D027963:Chloride-Bicarbonate Antiporters; C486743:Slc26a7 protein, mouse; D000076988:Sulfate Transporters