Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors. Mus musculus

The goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation. Here we report one such cell line [T6(6)] that gives rise to megakaryocytic leukemia (M7 leukemia) upon transplantation. Overall design: Since the leukemic cells were retrovirally tagged with a GFP reporter, we sorted GFP+ leukemic blasts and generated their expression profiles by microarray.

本研究旨在构建携带造血转录因子GATA1突变（又称GATA1s突变）的人类唐氏综合征（Down Syndrome, DS）巨核细胞白血病小鼠模型。我们通过以下步骤达成该目标：采用携带绿色荧光蛋白（GFP）标记的基于MSCV的逆转录病毒转导Gata1s突变的胎儿祖细胞，随后开展体外筛选以获得永生化细胞系，再通过移植进行体内筛选以获取转化细胞系。本文报道一株命名为[T6(6)]的细胞系，该细胞系移植后可诱发巨核细胞白血病（M7型白血病）。整体实验设计：鉴于白血病细胞携带有整合了GFP报告基因的逆转录病毒标记，我们分选得到GFP阳性的白血病母细胞，并通过基因芯片技术生成其基因表达谱。