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Molecular Cytogenetics

Erythroid defects and increased retrovirally-induced tumor formation in Evi1 transgenic mice

Leukemia volume 14, pages 1876–1884 (2000)Cite this article

Abstract

Aberrant expression of the Evi1 (ecotropic virus integration site 1) proto-oncogene has been associated with hematopoietic malignancies in both mice and man. To determine the effect of enforced expression of Evi1 in vivo, we developed a transgenic mouse model utilizing the murine Sca-1 (Ly-6E.1) promoter. Here, we describe the generation and analysis of three independent lines of Evi1 transgenic mice. Transgenic animals of two founder lines developed normally. These mice did not show any obvious hematological abnormalities but showed a significant reduction in the number of bone marrow colony-forming unit erythroid (CFU-E)-derived colonies. This implies a defect of normal erythroid hematopoiesis affecting relatively late erythroid progenitor cells. We also show that when newborn Evi1 transgenic mice of these two lines were infected with Cas-Br-M MuLV, tumor incidence was greatly enhanced in comparison with nontransgenic littermates, indicating an increased susceptibility for leukemia development. Interestingly, analysis of a third founder line revealed that all male progeny consistently displayed severely impaired erythropoiesis with major defects in the bone marrow, spleen and peripheral blood. Taken together, our results present the first evidence of Evi1 disturbing normal erythropoiesis in vivo and provides evidence for cooperative potential of Evi1 in tumor progression.

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Acknowledgements

We thank Dr Elaine Dzierzak for providing the Sca-1 (Ly-6E.1) cassette (pL6Cla), Dr Nico de Both for histopathological analysis, Dr Rosalyn Slater and Bep Smit for FISH analysis, Trudi Visser for technical assistance on colony cultures and Karola van Rooyen for preparation of figures. This work was supported by the Dutch Cancer Society (KWF), the Netherlands Organization for Scientific Research (NWO) and the Royal Dutch Academy of Sciences (KNAW).

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Authors and Affiliations

  1. Institute of Hematology, Faculty of Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands

    D Louz, M van den Broek, S Verbakel, Y Vankan, K van Lom, M Joosten, B Löwenberg & R Delwel

  2. Department of Cell Biology and Genetics, Faculty of Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands

    D Meijer

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  1. D Louz
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Louz, D., van den Broek, M., Verbakel, S. et al. Erythroid defects and increased retrovirally-induced tumor formation in Evi1 transgenic mice. Leukemia 14, 1876–1884 (2000). https://doi.org/10.1038/sj.leu.2401887

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