Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1).
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.
Kiyokawa
H
H
Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Kineman
R D
RD
Manova-Todorova
K O
KO
Soares
V C
VC
Hoffman
E S
ES
Ono
M
M
Khanam
D
D
Hayday
A C
AC
Frohman
L A
LA
Koff
A
A
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D006965:Hyperplasia; D007030:Hypothalamo-Hypophyseal System / Q000473:pathology / Q000503:physiopathology; D007247:Infertility, Female / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology*; D010053:Ovary / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases