A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice

M L Fero; M Rivkin; M Tasch; P Porter; C E Carow; E Firpo; K Polyak; L H Tsai; V Broudy; R M Perlmutter; K Kaushansky; J M Roberts

doi:10.1016/s0092-8674(00)81239-8

A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice

Cell. 1996 May 31;85(5):733-44. doi: 10.1016/s0092-8674(00)81239-8.

Authors

M L Fero¹, M Rivkin, M Tasch, P Porter, C E Carow, E Firpo, K Polyak, L H Tsai, V Broudy, R M Perlmutter, K Kaushansky, J M Roberts

Affiliation

¹ Department of Basic Sciences, Division of Public Health, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.

PMID: 8646781
DOI: 10.1016/s0092-8674(00)81239-8

Abstract

Targeted disruption of the murine p27(Kip1) gene caused a gene dose-dependent increase in animal size without other gross morphologic abnormalities. All tissues were enlarged and contained more cells, although endocrine abnormalities were not evident. Thymic hyperplasia was associated with increased T lymphocyte proliferation, and T cells showed enhanced IL-2 responsiveness in vitro. Thus, p27 deficiency may cause a cell-autonomous defect resulting in enhanced proliferation in response to mitogens. In the spleen, the absence of p27 selectively enhanced proliferation of hematopoietic progenitor cells. p27 deletion, like deletion of the Rb gene, uniquely caused neoplastic growth of the pituitary pars intermedia, suggesting that p27 and Rb function in the same regulatory pathway. The absence of p27 also caused an ovulatory defect and female sterility. Maturation of secondary ovarian follicles into corpora lutea, which express high levels of p27, was markedly impaired.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adenoma / genetics
Adenoma / pathology
Animals
Base Sequence
Cell Cycle Proteins*
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases / antagonists & inhibitors
DNA Primers / genetics
Enzyme Inhibitors / metabolism
Female
Gene Targeting
Gigantism / genetics*
Gigantism / pathology
Hyperplasia
Infertility, Female / genetics*
Infertility, Female / pathology
Lymphocyte Activation
Male
Mice
Mice, Knockout
Microtubule-Associated Proteins / deficiency*
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / physiology
Molecular Sequence Data
Pituitary Neoplasms / genetics*
Pituitary Neoplasms / pathology
Syndrome
T-Lymphocytes / immunology
Thymus Hyperplasia / genetics
Thymus Hyperplasia / immunology
Tumor Suppressor Proteins*

Substances

Cdkn1b protein, mouse
Cell Cycle Proteins
DNA Primers
Enzyme Inhibitors
Microtubule-Associated Proteins
Tumor Suppressor Proteins
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases

Grants and funding

etc