1. Arrest in Primitive Erythroid Cell Development Caused by Promoter-specific Disruption of the GATA-1 Gene
- Author
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Norio Hayashi, Satoru Takahashi, Masayuki Yamamoto, Naruyoshi Suwabe, Kou Onodera, Nobuaki Yanai, Yoichi Nabesima, and Hozumi Motohashi
- Subjects
Male ,Transgene ,Biology ,Polymerase Chain Reaction ,Biochemistry ,Germline ,Mice ,hemic and lymphatic diseases ,Animals ,Erythropoiesis ,GATA1 Transcription Factor ,RNA, Messenger ,Promoter Regions, Genetic ,Molecular Biology ,Gene ,Erythroid Precursor Cells ,Reporter gene ,Erythroid-Specific DNA-Binding Factors ,Nuclear Proteins ,Zinc Fingers ,Heterozygote advantage ,Cell Biology ,Embryonic stem cell ,Molecular biology ,DNA-Binding Proteins ,Haematopoiesis ,Phenotype ,embryonic structures ,Female ,Transcription Factors - Abstract
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.
- Published
- 1997
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