Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach.
Slc26a9 is a recently identified anion transporter that is abundantly expressed in gastric epithelial cells. To study its role in stomach physiology, gene targeting was used to prepare mice lacking Slc26a9. Homozygous mutant (Slc26a9(-/-)) mice appeared healthy and displayed normal growth. Slc26a9 deletion resulted in the loss of gastric acid secretion and a moderate reduction in the number of parietal cells in mutant mice at 5 weeks of age. Immunofluorescence labeling detected the H-K-ATPase exclusively on the apical pole of gastric parietal cells in Slc26a9(-/-) mice, in contrast to the predominant cytoplasmic localization in Slc26a9(+/+) mice. Light microscopy indicated that gastric glands were dilated, and electron micrographs displayed a distinct and striking absence of tubulovesicles in parietal cells and reductions in the numbers of parietal and zymogen cells in Slc26a9(-/-) stomach. Expression studies indicated that Slc26a9 can function as a chloride conductive pathway in oocytes as well as a Cl(-)/HCO(3)(-) exchanger in cultured cells, and localization studies in parietal cells detected its presence in tubulovesicles. We propose that Slc26a9 plays an essential role in gastric acid secretion via effects on the viability of tubulovesicles/secretory canaliculi and by regulating chloride secretion in parietal cells.
Xu
Jie
J
Research Services, Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.
Song
Penghong
P
Miller
Marian L
ML
Borgese
Frank
F
Barone
Sharon
S
Riederer
Brigitte
B
Wang
Zhaohui
Z
Alper
Seth L
SL
Forte
John G
JG
Shull
Gary E
GE
Ehrenfeld
Jordi
J
Seidler
Ursula
U
Soleimani
Manoocher
M
D000818:Animals; D000831:Animals, Newborn; D027321:Anion Transport Proteins / Q000378:metabolism; D017920:Antiporters / Q000172:deficiency* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000473:pathology*; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D005744:Gastric Acid / Q000378:metabolism*; D017353:Gene Deletion; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D064606:SLC4A Proteins; D000076988:Sulfate Transporters; D017186:Titrimetry; D014981:Xenopus
D027321:Anion Transport Proteins; D017920:Antiporters; D015415:Biomarkers; D064606:SLC4A Proteins; C533708:Slc26a9 protein, mouse; D000076988:Sulfate Transporters; D017506:H(+)-K(+)-Exchanging ATPase