Development of mice expressing a single D-type cyclin

Genes Dev. 2002 Dec 15;16(24):3277-89. doi: 10.1101/gad.1023602.


D-cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery. To directly test the ability of each D-cyclin to drive development of various lineages, we generated mice expressing only cyclin D1, or only cyclin D2, or only cyclin D3. We found that these "single-cyclin" embryos develop normally until late gestation. Our analyses revealed that in single-cyclin embryos, the tissue-specific expression pattern of D-cyclins was lost. Instead, mutant embryos ubiquitously expressed the remaining D-cyclin. These findings suggest that the functions of the three D-cyclins are largely exchangeable at this stage. Later in life, single-cyclin mice displayed focused abnormalities, resulting in premature mortality. "Cyclin D1-only" mice developed severe megaloblastic anemia, "cyclin D2-only" mice presented neurological abnormalities, and "cyclin D3-only" mice lacked normal cerebella. Analyses of the affected tissues revealed that these compartments failed to sufficiently up-regulate the remaining, intact D-cyclin. In particular, we found that in cerebellar granule neuron precursors, the N-myc transcription factor communicates with the cell cycle machinery via cyclins D1 and D2, but not D3, explaining the inability of D3-only mice to up-regulate cyclin D3 in this compartment. Hence, the requirement for a particular cyclin in a given tissue is likely caused by specific transcription factors, rather than by unique properties of cyclins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anemia, Megaloblastic / metabolism*
  • Anemia, Megaloblastic / pathology
  • Animals
  • Blotting, Western
  • Cell Cycle / physiology
  • Cell Division / physiology
  • Cerebellum / abnormalities*
  • Cerebellum / pathology
  • Cyclin D1 / physiology*
  • Cyclin D2
  • Cyclin D3
  • Cyclins / physiology*
  • Embryo, Mammalian / abnormalities
  • Embryonic and Fetal Development
  • Female
  • Genes, myc
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Knockout
  • Nervous System Diseases / metabolism*
  • Nervous System Diseases / pathology
  • Pregnancy
  • RNA, Messenger
  • Retinoblastoma Protein / metabolism
  • Retroviridae


  • Ccnd2 protein, mouse
  • Ccnd3 protein, mouse
  • Cyclin D2
  • Cyclin D3
  • Cyclins
  • RNA, Messenger
  • Retinoblastoma Protein
  • Cyclin D1