In vivo requirements for transcription factors GATA-1 and GATA-2 during hematopoiesis.

造血过程中转录因子 GATA-1 和 GATA-2 的体内需求。

• 批准号: 17590979
• 负责人: SHIMIZU Ritsuko
• 金额: $ 2.24万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590979/
• 关键词: GATA-1; GATA-2; Conditional knockout; Erythrocyte; Megakaryocyte; Hematopoietic stem cell; Proliferation and differentiation; 造血肝細胞

Firstly, we established GATA-1 conditional knockout mice (G1-CK0) and mated with Mx1-Cre mice to generate G1-CKO::Mx1-Cre. In these mice, the GATA-1 hematopoietic cell specific first exon (IE exon) could be effectively deleted in hematopoietic cells by using injected polyinosinic-polycytidylic acid (pIpC) to induce expression of Cre recombinase. One month after pIpC injection, G1-CKO::Mx1-Cre mice developed severe anemia and thrombocytopenia. Immunophenotypical examination revealed that c-Kit^-CD71^+Ter119^<low> immature erythroid progenitors and GATA-1 deficient megakaryocytes were accumulated in bone marrows and spleens.Secondary, We established and GATA-2 conditional knockout mice (G2-CKO) in which GATA-2 cDNA sandwiched between two loxP sequences was inserted into the translation initiation site of Oata2 gene. To investigate the function of GATA-2 on the hematopoietic cell proliferation in vivo, we established compound mice with Mx1-Cre (G2-CK0::Mx1-Cre) The number of Lin^-c-Kit^+Sca1^+ hematopoietic stem cells for the G2-CKO::Mx1-Cre mice significantly declined compared with those for the control mice after pIpC injection. These findings indicate that the maintenance of hematopoietic stem cells by GATA-2 and the regulation of erythroid/megakaryocytic cell development by GATA-1 are important for adult hematopoiesis.

首先，建立了加塔-1基因条件性敲除小鼠（G1-CK 0），并与Mx 1-Cre小鼠交配产生G1-CKO：：Mx 1-Cre。在这些小鼠中，通过注射多聚肌苷酸-多聚胞苷酸（pIpC）诱导Cre重组酶的表达，可以有效地在造血细胞中缺失加塔-1造血细胞特异性第一外显子（IE exon）。注射pIpC后1个月，G1-CKO：：Mx 1-Cre小鼠出现严重贫血和血小板减少症。免疫表型检查显示，骨髓和脾脏中聚集了c-Kit^-CD 71 ^+ Ter 119 ^<low>未成熟红系祖细胞和加塔-1缺陷型巨核细胞。其次，我们建立了GATA-2条件性基因敲除小鼠（G2-CKO），其中GATA-2 cDNA夹在两个loxP序列之间，插入Oata 2基因的翻译起始位点。为探讨加塔-2对造血细胞增殖的影响，我们建立了Mx 1-Cre（G2-CK 0：：Mx 1-Cre）复合小鼠模型。注射pIpC后，G2-CK 0：：Mx 1-Cre小鼠的Lin^-c-Kit^+ Sca 1 ^+造血干细胞数较对照组明显减少。这些发现表明，加塔-2对造血干细胞的维持和加塔-1对红系/巨核细胞发育的调节对于成人造血是重要的。

项目成果

Application of Modern Biotechnology and Mouse Genetics for the Study of Hematopoiesis

现代生物技术和小鼠遗传学在造血研究中的应用

• 发表时间: 2005
• 期刊: The Joint Meeting of the 67th Annual Meeting of Japanese Society of Hematology and the 47 the Annual Meeting of Japanese Society of Clinical Hematology Education Program Book
• 作者: Yamamoto;M.;et al.
• 通讯作者: et al.

A Gata2 intronic enhancer confers its pan-endothelia-specific regulation

• DOI: 10.1242/dev.001297
• 发表时间: 2007-05-01
• 期刊: DEVELOPMENT
• 影响因子: 4.6
• 作者: Khandekar, Melin;Brandt, William;Engel, James Douglas
• 通讯作者: Engel, James Douglas

Dynamic regulation of Gata factor levels is more important than their identity

• DOI: 10.1182/blood-2006-11-060491
• 发表时间: 2007-06-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Ferreira, Rita;Wai, Albert;Philipsen, Sjaak
• 通讯作者: Philipsen, Sjaak

Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells.

缺乏 N 指结构域的 GATA-1 突变体的转基因过度表达会导致小鼠红系细胞溶血综合征。

• 发表时间: 2005
• 期刊: Gene Cells 10
• 作者: Nakano;M.;et al.
• 通讯作者: et al.

Characterization of GATA-1+ hemangioblastic cells in the mouse embryo

• DOI: 10.1038/sj.emboj.7601480
• 发表时间: 2007-01-10
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Yokomizo, Tomomasa;Takahashi, Satoru;Yamamoto, Masayuki
• 通讯作者: Yamamoto, Masayuki