Overexpression of cyclin D1 moderately increases ploidy in megakaryocytes

Background and Objectives. Megakalyocytes undergo a unique cell cycle by wh ich they replicate their complete genome many times in the absence of cytok inesis, In the search for regulators of the endomitotic cell cycle, we prev iously produced mice transgenic for cyclin D3 to identify this cyclin as ab le to enhance ploidy and to increase the number of differentiated cells in the megakaryocytic lineage. Of the D-type cyclins, cyclin D3 and to a much lesser extent cyclin D1, are present in megakaryocytes undergoing endomitos is and these cyclins are, respectively, markedly and moderately upregulated following exposure to the ploidy-promoting factor, Mpl-ligand. Our objecti ve was to explore whether cyclin D1 can mimic the effect of cyclin D3 on pl oidy in megakalyocytes. Design and Methods. We generated transgenic mice overexpressing cyclin D1 i n megakaryocytes and analyzed megakaryocyte ploidy, number and platelet lev els in these mice and control mice. Results. We show that transgenic mice in which cyclin D1 is overexpressed i n megakaryocytes display higher ploidy level than the control mice, with no change in the number of differentiated cells of the megakaryocytic series, or in platelet level. Interpretation and Conclusions. Our models support a key role for D-type cy clins in the endomitotic cell cycle, and also indicate that although cyclin D3, from among the D cyclins, is unique in its high levels of expression i n megakaryocytes, it is not unique in its ability to promote polyploidizati on. (C) 2001, Ferrata Storti Foundation.