Transgenic Research

, Volume 14, Issue 5, pp 655–663 | Cite as

Gastric Pit Cell Hyperplasia and Glandular Atrophy in Carbonic Anhydrase IX Knockout Mice: Studies on Two Strains C57/BL6 and BALB/C

  • Mari LeppilampiEmail author
  • Tuomo J. Karttunen
  • Jyrki Kivelä
  • Marta Ortova Gut
  • Silvia Pastoreková
  • Jaromir Pastorek
  • Seppo Parkkila


Carbonic anhydrase (CA) isoenzyme IX is a hypoxia-inducible enzyme, which is expressed in the human and rodent gastrointestinal tract and overexpressed in several different tumors. Functionally, it has probably an effect on proliferation and differentiation of gastrointestinal epithelial cells. It may also participate in gastric morphogenesis, since a recent study has shown gastric pit cell hyperplasia and glandular atrophy in CA IX-knockout mice. However, it is not known whether CA IX produces morphological changes in the gastric mucosa, which can turn into a dysplasia or malignancy in the presence of some carcinogenic factors. High-salt diet is considered such a factor which has been shown to modulate Helicobacter pylori-associated carcinogenesis. We produced two strains of CA IX-knockout mice, C57/BL6 and BALB/c, and the mice ate either standard or high-salt feed for 20 weeks. Stomach samples were collected from 40 Car9/ knockout mice and 37 wildtype littermates, and the tissue sections were examined for histology. CA IX-deficiency caused gastric pit cell hyperplasia and glandular atrophy in both BALB/c and C57/BL6 strains. Excess dietary salt had no significant effect on the severity of pit cell hyperplasia. No dysplasia was found in any of the groups. In C57/BL6 mice, CA IX-deficiency was associated with gastric submucosal inflammation. The results indicate that CA IX-deficiency provides a useful model to study the mechanisms of gastric morphogenesis and epithelial integrity. Further studies are needed to see whether CA IX has a role in the regulation of immune response. The findings suggest that although CA IX-deficiency is not a tumor-promoting factor per se, it induces glandular atrophy in the body mucosa, a lesion which is considered to be a preneoplastic alteration in the stomach.


atrophy carbonic anhydrase hyperplasia knockout stomach 


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Copyright information

© Springer 2005

Authors and Affiliations

  • Mari Leppilampi
    • 1
    Email author
  • Tuomo J. Karttunen
    • 2
  • Jyrki Kivelä
    • 3
    • 4
  • Marta Ortova Gut
    • 5
  • Silvia Pastoreková
    • 6
  • Jaromir Pastorek
    • 6
  • Seppo Parkkila
    • 1
    • 7
  1. 1.Department of Clinical ChemistryUniversity of OuluOuluFinland
  2. 2.Department of PathologyUniversity of OuluOuluFinland
  3. 3.Institute of DentistryUniversity of HelsinkiHelsinkiFinland
  4. 4.Research Institute of Military MedicineCentral Military HospitalHelsinkiFinland
  5. 5.Department of Molecular GeneticsInstitute of Molecular Pharmacology and Medical Center of Free University of BerlinGermany
  6. 6.Centre of Molecular Medicine, Institute of VirologySlovak Academy of SciencesBratislavaSlovak Republic
  7. 7.Institute of Medical TechnologyUniversity of Tampere and Tampere University HospitalTampereFinland

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