Mice lacking a CDK inhibitor, p57Kip2, exhibit skeletal abnormalities and growth retardation.
p57Kip2, one of the cyclin-dependent kinase (CDK) inhibitors, has been suggested to be a tumor suppressor candidate. To elucidate its biological roles in mouse development and tumorigenesis, we created p57Kip2-deficient mice. The p57Kip2-deficient mice exhibited a cleft palate and defective bone formation resulting in severe dyspnea. Most of the p57Kip2-deficient mice died within 24 h after birth, while about 10% of them survived beyond the weaning period. All of the surviving mice showed severe growth retardation. The males showed immaturity of the testes, prostate and seminal vesicles, and the females showed vaginal atresia, immaturity of the uterus, and an increased number of atretic follicles. Although Yan et al. and Zhang et al. have already reported p57Kip2-deficient mice, they could not investigate the phenotypes of the surviving p57Kip2-deficient mice. Also, most of the symptoms of Beckwith-Wiedemann syndrome could not be reproduced in the mutant mice. Embryonic fibroblasts prepared from p57Kip2-deficient mice showed no differences in the proliferation rate and saturation density, suggesting that G1 arrest is largely independent of p57Kip2 function. Our results suggest that p57Kip2 plays a critical role in development, but do not support the hypothesis that the p57Kip2 gene is a tumor-suppressor gene or is responsible for Beckwith-Wiedemann syndrome.
Takahashi
K
K
Molecular Oncology Group, Nippon Roche Research Center, Kajiwara, Kamakura, Kanagawa 247-0063, Japan. takahask@pharm.showa-u.ac.jp
Nakayama
K
K
Nakayama
K
K
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology / Q000201:enzymology; D002478:Cells, Cultured; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D016193:G1 Phase / Q000235:genetics; D018390:Gene Targeting; D006130:Growth Disorders / Q000196:embryology* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics*; D010641:Phenotype
C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins