ENHANCED GROWTH OF MICE LACKING THE CYCLIN-DEPENDENT KINASE INHIBITORFUNCTION OF P27(KIP1)

Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enh ances growth of mice. Growth is attributed to an increase in cell numb er, due to increased cell proliferation, most obviously in tissues tha t ordinarily express p27 at the highest levels. Disruption of p27 func tion leads to nodular hyperplasia in the intermediate lobe of the pitu itary. However, increased growth occurs without an increase in the amo unts of either growth hormone or IGF-I. In addition, female mice were infertile. Luteal cell differentiation is impaired, and a disordered e strus cycle is detected. These results reflect a disturbance of the hy pothalamic-pituitary-ovarian axis. The phenotypes of these mice sugges t that loss of p27 causes an alteration in cell proliferation that can lead to specific endocrine dysfunction.