Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric.
The AE2 Cl-/HCO3- exchanger is expressed in numerous cell types, including epithelial cells of the kidney, respiratory tract, and alimentary tract. In gastric epithelia, AE2 is particularly abundant in parietal cells, where it may be the predominant mechanism for HCO3- efflux and Cl- influx across the basolateral membrane that is needed for acid secretion. To investigate the hypothesis that AE2 is critical for parietal cell function and to assess its importance in other tissues, homozygous null mutant (AE2(-/-)) mice were prepared by targeted disruption of the AE2 (Slc4a2) gene. AE2(-/-) mice were emaciated, edentulous (toothless), and exhibited severe growth retardation, and most of them died around the time of weaning. AE2(-/-) mice exhibited achlorhydria, and histological studies revealed abnormalities of the gastric epithelium, including moderate dilation of the gastric gland lumens and a reduction in the number of parietal cells. There was little evidence, however, that parietal cell viability was impaired. Ultrastructural analysis of AE2(-/-) gastric mucosa revealed abnormal parietal cell structure, with severely impaired development of secretory canaliculi and few tubulovesicles but normal apical microvilli. These results demonstrate that AE2 is essential for gastric acid secretion and for normal development of secretory canalicular and tubulovesicular membranes in mouse parietal cells.
Gawenis
Lara R
LR
Department of Molecular Genetics, Biochemistry and Microbiology, Unniversity of Cincinnati College of Medicine, Ohio 45267, USA.
Ledoussal
Clara
C
Judd
Louise M
LM
Prasad
Vikram
V
Alper
Seth L
SL
Stuart-Tilley
Alan
A
Woo
Alison L
AL
Grisham
Christina
C
Sanford
L Philip
LP
Doetschman
Thomas
T
Miller
Marian L
ML
Shull
Gary E
GE
D000126:Achlorhydria / Q000235:genetics; D000483:Alleles; D000818:Animals; D027321:Anion Transport Proteins; D017920:Antiporters; D015152:Blotting, Northern; D015153:Blotting, Western; D002470:Cell Survival; D027963:Chloride-Bicarbonate Antiporters; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009154:Mutation; D010295:Parietal Cells, Gastric / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D064606:SLC4A Proteins; D019076:Transgenes
D027321:Anion Transport Proteins; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; D012333:RNA, Messenger; D064606:SLC4A Proteins; C579495:Slc4a2 protein, mouse