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

Research output: Contribution to journalArticle

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 CD4-8+ 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.

Original languageEnglish (US)
Pages (from-to)S101-S105
JournalJournal of Clinical Immunology
Volume15
Issue number6 Supplement
DOIs
StatePublished - Nov 1995

Keywords

  • G protein
  • T cells
  • gene targeting
  • inflammatory bowel disease
  • transmembrane signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rudolph, U., Finegold, M. J., Rich, S. S., Harriman, G. R., Srinivasan, Y., Brabet, P., Bradley, A., & Birnbaumer, L. (1995). Gi2α protein deficiency: A model for inflammatory bowel disease. Journal of Clinical Immunology, 15(6 Supplement), S101-S105. https://doi.org/10.1007/BF01540899