Abstract
Mice lacking the imprinted Cdk inhibitor p57KIP2 have altered cell proliferation and differentiation, leading to abdominal muscle defects; cleft palate; endochondral bone ossification defects with incomplete differentiation of hypertrophic chondrocytes; renal medullary dysplasia; adrenal cortical hyperplasia and cytomegaly; and lens cell hyperproliferation and apoptosis. Many of these phenotypes are also seen in patients with Beckwith–Wiedemann syndrome, a pleiotropic hereditary disorder characterized by overgrowth and predisposition to cancer, suggesting that loss of p57KIP2 expression may play a role in the condition.
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References
1. Harper, J. W. & Elledge, S. J. Cdk inhibitors in development and cancer. Curr. Opin. Genet. Dev. 6,56-64 (1996). 2. Sherr, C. J. Cancer cell cycles. Science 274, 1672-1677 (1996). 3. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81, 323-330 (1995). 4. Serrano, M. et al. Role of the INK4a locus in tumor suppression and cell mortality. Cell 85, 27-37 (1996). 5. Parker, S. B. et al. p53-Independent expression of p21Clpl in muscle and other terminally differentiating cells. Science 267, 1024-1027 (1995). 6. Deng, C. et al. Mice lacking p2iapl/WAF1 undergo normal development, but are defective in Gl checkpoint control. Cell 82, 675-684 (1995). 7. Nakayama, K. et al. Mice lacking p27KIP1 display increased body size, multiple organ hyperplasia, retinal displasia, and pituitary tumors. Cell 85, 707-720 (1996). 8. Kiyokawa, H. et al. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27KIP1. Cell 85, 721-732 (1996). 9. Fero, M. L. et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kipl-deficient mice. Cell 85, 733-744 (1996). 10. Matsuoka, S. et al. p57KIP2, a structurally distinct member of the p21CIP1 Cdk-inhibitor family, is a candidate tumor suppressor gene. Genes Dev. 9, 650-662 (1995). 11. Lee, M. L. etal. Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev. 9, 639-649 (1995). 12. Hastie, N. D. The genetics of Wilms' tumor-a case of disrupted development. Annu. Rev. Genet. 28, 523-558 (1994). 13. Wiedemann, H. R. Tumours and hemihypertrophy associated with Wiedemann-Beckwith syndrome. Eur. J. Pediatr. 141, 129-134 (1983). 14. Junien, C. Beckwith-Wiedemann syndrome, tumourigenesis and imprinting. Curr. Opin. Biol. 2, 431-438 (1992). 15. Matsuoka, S. et al. Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor p57rap2, on chromosome llplS. Proc. Natl Acad. Sci. USA 93, 3026-3030 (1996). 16. Hatada, I. & Mukai, T. Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. Nature Genet. 11, 204-206 (1995). 17. Hoovers, J. et al Multiple genetic loci within Ilpl5.5 denned by Beckwith-Wiedemann Syndrome rearrangement breakpoints and subchromosomal transferable fragments. Proc. Natl Acad. Sci. USA 92, 12456-12460 (1995). 18. Hatada, I. et al An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome. Nature Genet. 14, 171-173 (1996). 19. Kaufman, M. H. The Atlas of Mouse Development (Academic, London, 1992). 20. Ferguson, M. J. W. Palate development. Development (suppl.) 103, 41-60 (1988). 21. Beckwith, B. Macroglossia, omphalocele, adrenal cytomegaly, gigantism, and hyperplastic visceromegaly. Birth Defects: Original Article Series 2 Vol. V No. 2 (ed. Bergsma, D.) 188-196 (The National Foundation, 1969). 22. Hepinstall, R. H. in Pathology of the Kidney Vol. 1, 114-155 (Little, Brown, Boston, MA, 1992). 23. Jacenko, O. et al. Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition. Nature 365, 56-61 (1993). 24. McAvoy, J. W. Induction of the eye lens. Differentiation 17, 137-149 (1996). 25. Morgenbesser, S. D. et al. p53-dependent apoptosis produced by Rb deficiency in the developing mouse lens. Nature 371, 72-74 (1994). 26. Cobrink, D. et al. Shared role of the Rb-related p!30 and p!07 proteins in limb development. Genes Dev. 10, 1633-1644 (1996). 27. Elliott, M. et al. Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases. Clin. Genet. 46, 168-174 (1994). 28. Takato, T., Kamei, M., Kato, K. & Kitano, I. Cleft palate in the Beckwith-Wiedemann syndrome. Ann. Plastic Surg. 22, 347-349 (1989). 29. Sotelo-Avila, C., Gonzalez-Crussi, F. & Fowler, J. W. Complete and incomplete forms of Beckwith-Wiedemann syndrome: their oncogenic potential/. Pediatr. 96, 47-50 (1980). 30. Leighton, P. A. et al Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375, 34-39 (1995). 31. Weksberg, R., Shem, D. R., Song, Q. L. & Squire, J, Disruption of IGF2 imprinting in Beckwith-Wiedemann Syndrome. Nature Genet. 5, 143-149 (1993). 32. Ramirez-Solis, R. et al. Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments. Cell 73, 279-294 (1993). 33. Dynlacht, B. D. et al. Purification and analysis of CIP/KIP proteins. Methods Enzymol. (in the press).
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Zhang, P., Liégeois, N., Wong, C. et al. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith–Wiedemann syndrome. Nature 387, 151–158 (1997). https://doi.org/10.1038/387151a0
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DOI: https://doi.org/10.1038/387151a0
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