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Molecular and Cellular Biology, February 2005, p. 1081-1088, Vol. 25, No. 3
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.3.1081-1088.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Genetic Replacement of Cyclin D1 Function in Mouse Development by Cyclin D2

Bradley C. Carthon,^1,2,3 Carola A. Neumann,^1,2 Manjusri Das,^1,2 Basil Pawlyk, Tiansen Li,⁴ Yan Geng,^1,2 and Piotr Sicinski^1,2,3*

Department of Cancer Biology, Dana-Farber Cancer Institute,¹ Department of Pathology,² Program in Biomedical and Biological Sciences,³ Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts⁴

Received 14 July 2004/ Returned for modification 19 August 2004/ Accepted 18 October 2004

D cyclins (D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. It is unclear whether each of the D cyclins performs unique, tissue-specific functions or the three proteins have virtually identical functions and differ mainly in their pattern of expression. We previously generated mice lacking cyclin D1, and we observed that these animals displayed hypoplastic retinas and underdeveloped mammary glands and a presented developmental neurological abnormality. We now asked whether the specific requirement for cyclin D1 in these tissues reflected a unique pattern of D cyclin expression or the presence of specialized functions for cyclin D1 in cyclin D1-dependent compartments. We generated a knock-in strain of mice expressing cyclin D2 in place of D1. Cyclin D2 was able to drive nearly normal development of retinas and mammary glands, and it partially replaced cyclin D1's function in neurological development. We conclude that the differences between these two D cyclins lie mostly in the tissue-specific pattern of their expression. However, we propose that subtle differences between the two D cyclins do exist and they may allow D cyclins to function in a highly optimized fashion. We reason that the acquisition of multiple D cyclins may allow mammalian cells to drive optimal proliferation of a diverse array of cell types.

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* Corresponding author. Mailing address: Department of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: (617) 632-5005. Fax: (617) 632-5006. E-mail: peter_sicinski{at}dfci.harvard.edu.

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Molecular and Cellular Biology, February 2005, p. 1081-1088, Vol. 25, No. 3
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.3.1081-1088.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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