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，我们建立了GATA-1条件基因敲除小鼠（G1-CK0），并与MX1-CRE小鼠交配以生成G1-CKO :: MX1-CRE。在这些小鼠中，通过使用注射的聚精毒素多胞分酸（PIPC）诱导CRE重组酶的表达，可以在造血细胞中有效地删除造血细胞中的GATA-1造血细胞特异性第一外显子（IE外显子）。 PIPC注射后一个月，G1-CKO :: MX1-CRE小鼠出现严重的贫血和血小板减少症。免疫表型检查表明，C-KIT^-CD71^+TER119^<low>未成熟的红细胞祖细胞和GATA-1不足的巨核细胞积累在骨骨髓和脾脏中。其中将夹在两个LOXP序列之间的GATA-2 cDNA插入了OATA2基因的翻译起始位点。为了研究GATA-2在体内造血细胞增殖上的功能，我们用MX1-CRE（G2-CK0 :: MX1-CRE）建立了复合小鼠的lin^-c-kit^+ sca1^+ sca1^+造血茎的数量与PIPC注射后的对照小鼠相比，G2-CKO :: MX1-CRE小鼠的细胞显着下降。这些发现表明，通过GATA-2维持造血干细胞，以及通过GATA-1通过GATA-1发育的红细胞/巨核细胞发育对成人造血对象很重要。

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

Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway

• DOI: 10.1111/j.1365-2443.2005.00864.x
• 发表时间: 2005-07-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Minegishi, N;Suzuki, N;Yamamoto, M
• 通讯作者: Yamamoto, M

GATA-1 self-association controls erythroid development in vivo

• DOI: 10.1074/jbc.m701936200
• 发表时间: 2007-05-25
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Shimizu, Ritsuko;Trainor, Cecelia D.;Yamamoto, Masayuki
• 通讯作者: Yamamoto, Masayuki

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