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Journal of Clinical Immunology

, Volume 15, Supplement 6, pp S101–S105 | Cite as

Gi2α protein deficiency: A model for inflammatory bowel disease

  • Uwe Rudolph
  • Milton J. Finegold
  • Susan S. Rich
  • Gregory R. Harriman
  • Yogambal Srinivasan
  • Philippe Brabet
  • Allan Bradley
  • LUTZ Birnbaumer
The Role of Superantigens in Disease and Animal Models as Instructional Paradigms of Human Disease

Abstract

Mice deficient for the G protein subunit Gi2α were obtained by gene targeting. They displayed a growth retardation that was apparent at 6 weeks of age. They subsequently developed diffuse colitis with clinical and histopathological features closely resembling those of ulcerative colitis in humans. Seven of 20 Gi2α-deficient mice with colitis also developed adenocarcinomas of the colon. Gi2α-deficient thymocytes displayed two-to fourfold increases in mature CD4+8 and CD48+ phenotypes, an approximately threefold increase in highintensity CD3 staining and enhanced proliferative responses to T-cell receptor stimuli. Stimulation of Gi2α-deficient peripheral T cells induced a hyperresponsive profile of interleukin-2, tumor necrosis factor, and interferon-γ production, which may reflect a heightened response of primed cells or a defective negative regulation. We suggest that Gi2α-deficient mice may represent a useful animal model for dissecting the pathomechanisms of inflammatory bowel disease and also for the development of novel therapeutic strategies.

Key words

G protein transmembrane signaling gene targeting inflammatory bowel disease T cells 

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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Uwe Rudolph
    • 1
    • 5
  • Milton J. Finegold
    • 2
  • Susan S. Rich
    • 3
  • Gregory R. Harriman
    • 4
  • Yogambal Srinivasan
    • 1
  • Philippe Brabet
    • 1
  • Allan Bradley
    • 8
    • 9
  • LUTZ Birnbaumer
    • 1
    • 4
    • 6
    • 7
  1. 1.Departments of Cell BiologyBaylor College of MedicineHouston
  2. 2.Department of PathologyBaylor College of MedicineHouston
  3. 3.Department of Microbiology & ImmunologyBaylor College of MedicineHouston
  4. 4.Department of MedicineBaylor College of MedicineHouston
  5. 5.Department of PharmacologyBaylor College of MedicineHouston
  6. 6.Departrnent of Molecular Physiology & BiophysicsBaylor College of MedicineHouston
  7. 7.Division of NeuroscienceBaylor College of MedicineHouston
  8. 8.Institute of Molecular GeneticsBaylor College of MedicineHouston
  9. 9.Howard Hughes Medical InstituteBaylor College of MedicineHouston

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