A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice.
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.
Fero
M L
ML
Department of Basic Sciences, Division of Public Health, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Rivkin
M
M
Tasch
M
M
Porter
P
P
Carow
C E
CE
Firpo
E
E
Polyak
K
K
Tsai
L H
LH
Broudy
V
V
Perlmutter
R M
RM
Kaushansky
K
K
Roberts
J M
JM
D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D017931:DNA Primers / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D005877:Gigantism / Q000235:genetics* / Q000473:pathology; D006965:Hyperplasia; D007247:Infertility, Female / Q000235:genetics* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology; D013952:Thymus Hyperplasia / Q000235:genetics / Q000276:immunology; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases