title: Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Molecular Genetics, Institute of Molecular Pharmacology and Medical Center of Free University of Berlin, Germany.
authors.forename: Marta Ortova
authors.initials: MO
authors.lastname: Gut
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
authors.forename: Zdeòka
authors.initials: Z
authors.lastname: Vernerová
authors.forename: Elvira
authors.initials: E
authors.lastname: Rohde
authors.forename: Jan
authors.initials: J
authors.lastname: Závada
authors.forename: Michael
authors.initials: M
authors.lastname: Höcker
authors.forename: Jaromír
authors.initials: J
authors.lastname: Pastorek
authors.forename: Tuomo
authors.initials: T
authors.lastname: Karttunen
authors.forename: Adriana
authors.initials: A
authors.lastname: Gibadulinová
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Závadová
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Knobeloch
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Jan
authors.initials: J
authors.lastname: Svoboda
authors.forename: Ivan
authors.initials: I
authors.lastname: Horak
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastoreková
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004573:Electrolytes / Q000097:blood; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D006965:Hyperplasia; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D013270:Stomach / Q000473:pathology*; D013272:Stomach Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: C404398:CAR90 protein, Phytophthora infestans; D018076:DNA, Complementary; D004573:Electrolytes; D005656:Fungal Proteins