Open AccessA New Transgenic Mouse Model for the Study of Cell Cycle Control in Megakaryocytes
Author(s) -
Thompson Alexander,
Zhao Zhuhui,
Ladd Daniel,
Zimmet Jeffrey,
Ravid Katya
Publication year - 1996
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.5530140723
Subject(s) - biology , haematopoiesis , megakaryocyte , cell cycle , transgene , bone marrow , microbiology and biotechnology , genetically modified mouse , stem cell factor , stem cell , progenitor cell , cellular differentiation , cancer research , immunology , cell , gene , genetics
During the development of the megakaryocyte lineage, the megakaryoblasts give rise to megakaryocytes which undergo repeated S phases in the absence of cytokinesis (endomitosis). The cellular oncogene myc plays a central role in the proliferation and differentiation of several cell types. In a previous study, we generated transgenic mice carrying c‐ myc fused to the estrogen receptor under the control of the platelet factor four (PF4) megakaryocyte‐specific promoter. The bone marrow of female transgenic mice, but not of male mice, displayed increased megakaryopoiesis. Here we report that β‐estradiolinduced activation of c‐ myc in cultured bone marrow cells derived from male or female transgenic mice resulted in prolonged survival of the cells in vitro. Addition of a cocktail of hemopoietic growth factors to β‐estradiol‐treated cells, including interleukin 6 (IL‐6), IL‐3 and stem cell factor further improved the survival time in culture and increased the percentage of large mature cells, but did not result in immortalization. The majority of these PF4‐expressing cells, however, did not reach the differentiation stage at which acetylcholinesterase is expressed and did not appear as large megakaryocytes. We conclude that cultured megakaryocytes overexpressing myc are induced to proliferate, but have a limited potential to fully differentiate. Under these conditions, cyclin D3 was downregulated while the level of cyclin A was slightly upregulated.