Scott E W, Simon M C, Anastasi J, Singh H
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, IL 60637.
Science. 1994 Sep 9;265(5178):1573-7. doi: 10.1126/science.8079170.
The transcription factor PU.1 is a hematopoietic-specific member of the ets family. Mice carrying a mutation in the PU.1 locus were generated by gene targeting. Homozygous mutant embryos died at a late gestational stage. Mutant embryos produced normal numbers of megakaryocytes and erythroid progenitors, but some showed an impairment of erythroblast maturation. An invariant consequence of the mutation was a multilineage defect in the generation of progenitors for B and T lymphocytes, monocytes, and granulocytes. Thus, the developmental programs of lymphoid and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor.
转录因子PU.1是ets家族的造血特异性成员。通过基因靶向产生了在PU.1基因座携带突变的小鼠。纯合突变胚胎在妊娠后期死亡。突变胚胎产生的巨核细胞和红系祖细胞数量正常,但有些显示出成红细胞成熟受损。该突变的一个不变结果是B和T淋巴细胞、单核细胞和粒细胞祖细胞生成中的多谱系缺陷。因此,淋巴系和髓系谱系的发育程序需要一种可能在多能祖细胞水平起作用的共同遗传功能。