ULCERATIVE-COLITIS AND ADENOCARCINOMA OF THE COLON IN G-ALPHA(I2)-DEFICIENT MICE

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 alpha(i2) (G a lpha(i2)) by homologous recombination in embryonic stem cells. G alpha (i2)-deficient mice display growth retardation and develop a lethal di ffuse colitis with clinical and histopathological features closely res embling ulcerative colitis in humans, including the development of ade nocarcinoma of the colon. Prior to clinical symptoms, the mice show pr ofound 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.