Abstract
Mice deficient for the G protein subunit Gi2 α 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 Gi2 α-deficient mice with colitis also developed adenocarcinomas of the colon. Gi2 α-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 Gi2 α-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 Gi2 α-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.
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Rudolph, U., Finegold, M.J., Rich, S.S. et al. Gi2α protein deficiency: A model for inflammatory bowel disease. J Clin Immunol 15 (Suppl 6), S101–S105 (1995). https://doi.org/10.1007/BF01540899
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DOI: https://doi.org/10.1007/BF01540899