Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene
Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene
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DOI：
10.1074/jbc.272.19.12611
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发表时间：
1997-05-09
影响因子：
4.8
通讯作者：
Yamamoto, M
中科院分区：
文献类型：
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作者：
Takahashi, S;Onodera, K;Yamamoto, M
为了阐明GATA-1在造血过程中的体内功能，我们特意破坏了胚胎干细胞中GATA-1基因的红系启动子并产生了种系嵌合体。携带靶向突变的嵌合体的雄性后代被发现在性交后 12.5 天因严重贫血而死亡，而杂合雌性则表现出从严重贫血到正常红细胞生成的特征。当雌性杂合子与携带报告基因（特异性标记原始红系祖细胞）的转基因雄性杂交时，在GATA-1突变胚胎的卵黄囊中观察到大量未分化红系细胞的积累，这表明GATA-1是体内原始红系细胞终末分化所必需的。
To elucidate the in vivo function of GATA-1 during hematopoiesis, we specifically disrupted the erythroid promoter of the GATA-1 gene in embryonic stem cells and generated germ line chimeras. Male offspring of chimeras bearing the targeted mutation were found to die by 12.5 days post coitus due to severe anemia while heterozygous females displayed characteristics ranging from severe anemia to normal erythropoiesis. When female heterozygotes were crossed with transgenic males carrying a reporter gene, which specifically marks primitive erythroid progenitors, massive accumulation of undifferentiated erythroid cells were observed in the yolk sacs of the GATA-1-mutant embryos, demonstrating that GATA-1 is required for the terminal differentiation of primitive erythroid cells in vivo.