Mice Lacking p27(Kip1) Display Increased Body Size, Multiple Organ Hyperplasia, Retinal Dysplasia, and Pituitary Tumors

Cell. 1996 May 31;85(5):707-20. doi: 10.1016/s0092-8674(00)81237-4.

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
  • Cell Division / 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*
  • Microtubule-Associated Proteins / physiology
  • Molecular Sequence Data
  • Phenotype
  • Pituitary Neoplasms / genetics*
  • Polyenes / pharmacology
  • Retinal Dysplasia / genetics*
  • Sirolimus
  • Tissue Distribution
  • Transforming Growth Factor alpha / pharmacology
  • Tumor Suppressor Proteins*

Substances

  • 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