TY - JOUR
T1 - Gi2α protein deficiency
T2 - A model for inflammatory bowel disease
AU - Rudolph, Uwe
AU - Finegold, Milton J.
AU - Rich, Susan S.
AU - Harriman, Gregory R.
AU - Srinivasan, Yogambal
AU - Brabet, Philippe
AU - Bradley, Allan
AU - Birnbaumer, Lutz
PY - 1995/11
Y1 - 1995/11
N2 - 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.
AB - 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.
KW - G protein
KW - T cells
KW - gene targeting
KW - inflammatory bowel disease
KW - transmembrane signaling
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U2 - 10.1007/BF01540899
DO - 10.1007/BF01540899
M3 - Article
C2 - 8613481
AN - SCOPUS:0028971299
VL - 15
SP - S101-S105
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
SN - 0271-9142
IS - 6 Supplement
ER -