title: Gi2 alpha protein deficiency: a model of inflammatory bowel disease.
abstract: Mice deficient for the G protein subunit Gi2 alpha 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 alpha-deficient mice with colitis also developed adenocarcinomas of the colon. Gi2 alpha-deficient thymocytes displayed two- to fourfold increases in mature CD4+8- and CD4-8+ phenotypes, an approximately threefold increase in high-intensity CD3 staining and enhanced proliferative responses to T-cell receptor stimuli. Stimulation of Gi 2 alpha-deficient peripheral T cells induced a hyperresponsive profile of interleukin-2, tumour necrosis factor, and interferon-gamma production, which may reflect a heightened response of primed cells or a defective negative regulation. We suggest that Gi 2 alpha-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.
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: U
authors.initials: U
authors.lastname: Rudolph
authors.forename: M J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: S S
authors.initials: SS
authors.lastname: Rich
authors.forename: G R
authors.initials: GR
authors.lastname: Harriman
authors.forename: Y
authors.initials: Y
authors.lastname: Srinivasan
authors.forename: P
authors.initials: P
authors.lastname: Brabet
authors.forename: A
authors.initials: A
authors.lastname: Bradley
authors.forename: L
authors.initials: L
authors.lastname: Birnbaumer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D018390:Gene Targeting; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D019204:GTP-Binding Proteins