NUP98-PMX1转基因小鼠发生髓系白血病样表型

Development of human myeloid leukemia-like phenotype in NUP98-PMX1 transgenic mice

目的 在整体动物水平研究NUP98 PMX1融合蛋白的致白血病作用。方法 采用分子克隆技术构建含有NUP98 PMX1的转基因质粒 ,显微注射法建立转NUP98 PMX1基因的小鼠 ,以PCR、RT PCR方法检测融合基因的表达 ;用流式细胞仪检测骨髓细胞表型。结果 转染NUP98 PMX1融合基因的NIH3T3细胞生长加快 ,软琼脂上可形成集落 ,并使裸鼠致瘤。出现病态的 8只NUP98 PMX1转基因小鼠中有 4只发生粒细胞白血病样表型 ,其中 3只表现为人类慢性髓系白血病样表型。结论 NUP98 PMX1融合基因具有致瘤性 ,其表达在髓系白血病的发生中起着极为重要的作用。

Objective In order to investigate the leukemogenic potential of NUP98 PMX1 fusion gene in vivo. Methods NUP98 PMX1 transgenic mice were generated, in which the fusion gene was driven by hCG promoter and expressed in myeloid cells at early stage of differentiation. Molecular cloning technology was used to construct NUP98 PMX1 transgenic plasmid. The genotype and phenotype of the NUP98 PMX1 transgenic mice were analyzed by PCR, RT PCR, peripheral blood count (PBC), bone marrow (BM) cells morphology and pathological examination. Results NIH3T3 cells transfected with NUP98 PMX1 fusion gene grew faster, formed colonies in soft agar, and developed tumors in 10 inoculated nude mice. Among 8 disordered NUP98 PMX1 transgenic mice, 4 developed myeloid leukemia like phenotype, including 3 resembling human chronic myeloid leukemia. Conclusion NUP98 PMX1 has oncogenic activity and plays a crucial role in leukemogenesis.