Mammalian Development and Cancer: A Brief History of Mice Lacking D-Type Cyclins or CDK4/CDK6

  • Ilona Kalaszczynska
  • Maria A. CiemerychEmail author
Part of the Current Cancer Research book series (CUCR)


Cellular proliferation is controlled by the orchestrated action of many cell cycle regulators. Among them are cyclins and cyclin-dependent kinases (CDKs), the activity of which is necessary to drive each phase of the cell cycle. Mitogenic stimulation leads to the expression of D cyclins which bind and activate CDK4 and CDK6. This event triggers a chain of events ultimately leading to cell division. Dissection of the functions of D cyclins and CDK4 in the regulation of proliferation of mammalian cells was greatly facilitated by the generation of genetically modified mice in which either D cyclins, their CDK partners, or other cell cycle regulators were ablated or replaced. In general, variable impact of germline loss of these cell cycle regulators on different tissues underscores specific roles for D cyclins and their partner CDKs in differentiation and development. These mouse models have also proved crucial for studies analyzing tumor development and for the discovery and evaluation of anticancer therapies, often linking tissue-specific functions to antineoplastic effects of inhibition of cyclin-D-dependent processes. This chapter summarizes the history of mice lacking D cyclins and CDK4/CDK6 and presents a synopsis of key findings from those animal models.


Mammals Mice Knock-out mice Knock-in mice Cell cycle Cyclin D CDK4 CDK6 Embryogenesis Cancer 



We want to thank Piotr Sicinski for being our mentor in the cyclin universe. We are also grateful to Katarzyna Koziak and Phil Hinds for their help at the very final stage of the manuscript preparation. During the preparation of this chapter, IK was supported by the Medical University of Warsaw statutory grant 1M15/N/2015 and the National Centre for Research and Development (NCBR) grant STRATEGMED3/307326/6/NCBR/2017 and MAC by the Faculty of Biology University of Warsaw funding 501/56/169600 and the National Science Centre Poland (NCN) grant 2012/05/N/NZ3/00314.


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Histology and Embryology, Center for Biostructure ResearchMedical University of WarsawWarsawPoland
  2. 2.Centre for Preclinical Research and TechnologyWarsawPoland
  3. 3.Department of Cytology, Institute of Zoology, Faculty of BiologyUniversity of WarsawWarsawPoland

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