Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9

Gastroenterology. 2002 Dec;123(6):1889-903. doi: 10.1053/gast.2002.37052.


Background & aims: Carbonic anhydrase (CA) IX is a highly active enzyme with adhesion capacity that is functionally implicated in acid-base balance and intercellular communication. It is normally present in basolateral membranes of gastrointestinal epithelial cells and ectopically expressed in various carcinomas. To show its physiologic relevance, we have cloned the Car9 gene and generated CA IX-deficient mice.

Methods: The mice with null mutation of the Car9 gene were obtained by targeted gene disruption. Tissue architecture and expression of markers were determined by histochemical and immunohistochemical techniques.

Results: Mice homozygous for the mutation developed gastric hyperplasia of the glandular epithelium with numerous cysts. The first changes were observed in the newborn animals, and the hyperplasia became prominent at the end of gastric morphogenesis in 4-week-old mice. Loss of CA IX led to overproduction of mucus-secreting pit cells and depletion of pepsinogen-positive chief cells. The proportion of H(+)/K(+)-adenosine triphosphatase-positive parietal cells significantly decreased, but their absolute number was not reduced. Correspondingly, CA IX-deficient mice had normal gastric pH, acid secretion, and serum gastrin levels.

Conclusions: Phenotypic consequences of the Car9 null mutation show the important role of CA IX in morphogenesis and homeostasis of the glandular gastric epithelium via the control of cell proliferation and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium
  • Animals
  • Cell Adhesion / physiology
  • Cell Death / physiology
  • Cell Division
  • Cell Line
  • DNA, Complementary / genetics
  • Electrolytes / blood
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gastric Acid / metabolism
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastric Mucosa / physiopathology
  • Hydrogen-Ion Concentration
  • Hyperplasia
  • Mice
  • Mice, Knockout / genetics
  • Mutation / physiology
  • Phenotype
  • Stomach / pathology*
  • Stomach Diseases / etiology*
  • Stomach Diseases / genetics
  • Stomach Diseases / pathology
  • Stomach Diseases / physiopathology


  • CAR90 protein, Phytophthora infestans
  • DNA, Complementary
  • Electrolytes
  • Fungal Proteins