Nature Genetics
10, 143 - 150 (1995)
doi:10.1038/ng0695-143
Ulcerative colitis and adenocarcinoma of the colon in G i2-deficient miceUwe Rudolph1, 2, 10, Milton J. Finegold3, Susan S. Rich4, Gregory R. Harriman5, Yogambal Srinivasan1, Philippe Brabet1, 11, Guylain Boulay1, 12, Allan Bradley8, 9
& Lutz Birnbaumer1, 5, 6, 7, 12
1Departments of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
2Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
3Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
4Department of Microbiology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
5Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
6Department of Molecular Physiology & Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
7Department of Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
8Department of Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
9Department of Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
10Present address: Institute of Pharmacology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
11Present address: Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Rue de la Cardonille, 34094 Montpellier Cedex 2, France
12Present address: Department of Anesthesiology, UCLA School of Medicine, Center for the Health Sciences, 10833 Le Conte Avenue, Los Angeles, California 90095-1778, USA Correspondence should be addressed to U.R. or L.B. G proteins are involved in cellular signalling and regulate a variety of biological processes including differentiation and development. We have generated mice deficient for the G protein subunit  i2 (Gi2) by homologous recombination in embryonic stem cells. Gi2−deficient mice display growth retardation and develop a lethal diffuse colitis with clinical and histopathological features closely resembling ulcerative colitis in humans, including the development of adenocarcinoma of the colon. Prior to clinical symptoms, the mice show profound alterations in thymocyte maturation and function. The study of these animals should provide important insights into the pathogenesis of ulcerative colitis as well as carcinogenesis.
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