MICE LACKING P27(KIP1) DISPLAY INCREASED BODY-SIZE, MULTIPLE ORGAN HYPERPLASIA, RETINAL DYSPLASIA, AND PITUITARY-TUMORS

Mice lacking p27(Kip1) have been created by gene targeting in embryoni c stem cells. These mice are larger than the control animals, with thy mus, pituitary, and adrenal glands and gonadal organs exhibiting strik ing enlargement. CDK2 activity is elevated about 10-fold in p27(-/-) t hymocytes. Development of ovarian follicles seems to be impaired, resu lting in female sterility. Similar to mice with the Rb mutation, the p 27(-/-) mice often develop pituitary tumors spontaneously. The retinas of the mutant mice show a disturbed organization of the normal cellul ar layer pattern. These findings indicate that p27(Kip1) acts to regul ate the growth of a variety of cells. Unexpectedly, the cell cycle arr est mediated by TGF beta, rapamycin, or contact inhibition remained in tact in p27(-/-) cells, suggesting that p27(Kip1) is not required in t hese pathways.