Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors.

Cell ·Vol. 85 ·No. 5 ·1996-05-31 ·Pages 707-20

Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shishido N, Horii I, Loh DY, Nakayama K

Abstract

Mice lacking p27(Kip1) have been created by gene targeting in embryonic stem cells. These mice are larger than the control animals, with thymus, pituitary, and adrenal glands and gonadal organs exhibiting striking enlargement. CDK2 activity is elevated about 10-fold in p27(-/-) thymocytes. Development of ovarian follicles seems to be impaired, resulting in female sterility. Similar to mice with the Rb mutation, the p27(-/-) mice often develop pituitary tumors spontaneously. The retinas of the mutant mice show a disturbed organization of the normal cellular layer pattern. These findings indicate that p27(Kip1) acts to regulate the growth of a variety of cells. Unexpectedly, the cell cycle arrest mediated by TGFbeta, rapamycin, or contact inhibition remained intact in p27(-/-) cells, suggesting that p27(Kip1) is not required in these pathways.

MeSH Terms

Animals Base Sequence Body Constitution/genetics Cell Cycle/genetics Cell Cycle Proteins Cell Division/drug effects,genetics Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases/antagonists & inhibitors DNA Primers/genetics DNA, Complementary/genetics Enzyme Inhibitors/metabolism Female Gene Expression Gene Targeting Genes, Tumor Suppressor Heterozygote Hyperplasia Infertility, Female/genetics Male Mice Mice, Knockout Microtubule-Associated Proteins/genetics,physiology Molecular Sequence Data Phenotype Pituitary Neoplasms/genetics Polyenes/pharmacology Retinal Dysplasia/genetics Sirolimus Tissue Distribution Transforming Growth Factor alpha/pharmacology Tumor Suppressor Proteins

Chemicals

Cdkn1b protein, mouse Cell Cycle Proteins DNA Primers DNA, Complementary Enzyme Inhibitors Microtubule-Associated Proteins Polyenes Transforming Growth Factor alpha Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases Sirolimus

Authors & Affiliations

9 authors, click to expand affiliations / ORCID

Nakayama K

Department of Biology, Nippon Roche Research Center, Kamakura, Kanagawa, Japan.

Ishida N

Shirane M

Inomata A

Inoue T

Shishido N

Horii I

Loh D Y

Nakayama K

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81237-4

Published

1996-05-31

Pages

707-20

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81237-4 View journal details

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Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors.

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