Development of mice expressing a single D-type cyclin.

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Animal, Blotting-Western, Cell-Cycle, Cell-Division, Cerebellum, Cyclin-D1, Cyclins, Embryo, Embryo-and-Fetal-Development, Female, Genes-myc, In-Situ-Hybridization, Male, Mice, Mice-Knockout, Nervous-System-Diseases, Pregnancy, RNA-Messenger, Retinoblastoma-Protein, Retroviridae, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

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Genes Dev 2002 Dec; 16(24):3277-89.


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.