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Publication : Development of mice expressing a single D-type cyclin.

First Author  Ciemerych MA Year  2002
Journal  Genes Dev Volume  16
Issue  24 Pages  3277-89
PubMed ID  12502747 Mgi Jnum  J:80994
Mgi Id  MGI:2447928 Doi  10.1101/gad.1023602
Citation  Ciemerych MA, et al. (2002) Development of mice expressing a single D-type cyclin. Genes Dev 16(24):3277-89
abstractText  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.
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