Enhanced Growth of Mice Lacking the Cyclin-Dependent Kinase Inhibitor Function of p27

TLDR

Disruption of the cyclin‑dependent kinase‑inhibitory domain of p27 enhances mouse growth by increasing cell proliferation, particularly in tissues with high p27 expression, causing nodular hyperplasia in the pituitary while not elevating growth hormone or IGF‑I levels. Female mice lacking p27 function are infertile, exhibit impaired luteal cell differentiation, a disordered estrus cycle, and disturbances in the hypothalamic‑pituitary‑ovarian axis, indicating that loss of p27 alters cell proliferation and leads to specific endocrine dysfunction.

Abstract

Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase in cell number, due to increased cell proliferation, most obviously in tissues that ordinarily express p27 at the highest levels. Disruption of p27 function leads to nodular hyperplasia in the intermediate lobe of the pituitary. However, increased growth occurs without an increase in the amounts of either growth hormone or IGF-I. In addition, female mice were infertile. Luteal cell differentiation is impaired, and a disordered estrus cycle is detected. These results reflect a disturbance of the hypothalamic-pituitary-ovarian axis. The phenotypes of these mice suggest that loss of p27 causes an alteration in cell proliferation that can lead to specific endocrine dysfunction.