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Blimp-1基因调控区域指导小鼠多种造血谱系和睾丸中的EGFP表达。

The Blimp-1 gene regulatory region directs EGFP expression in multiple hematopoietic lineages and testis in mice.

作者信息

Wang Dingyan, Zhuang Lihua, Gao Bo, Shi Chang-Xin, Cheung Joseph, Liu Mingyao, Jin Tianru, Wen Xiao-Yan

机构信息

Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, 620 University Avenue, Room 8-205, Toronto, ON, Canada, M5G 2C1.

出版信息

Transgenic Res. 2008 Apr;17(2):193-203. doi: 10.1007/s11248-007-9140-9. Epub 2007 Sep 19.

Abstract

The B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor involved in B cell terminal differentiation. Recent studies suggest that it also plays roles in the differentiation of myeloid and T cells. Using reporter gene analysis, we found that the mouse Blimp-1 promoter constructs of 4.4 kb, 2.5 kb and 1.6 kb exerted similar transcription activity in vitro. To study the Blimp-1 promoter function in vivo, we generated a mouse transgenic line in which the expression of EGFP is driven by the 4.4 kb Blimp-1 promoter fragment. EGFP expression was detected in multiple hematopoietic lineages including hematopoietic progenitor cells (c-kit+), B cells at various developmental stages (B220+, IgM+, IgD+ and CD138+), myeloid cells (Gr1+ and CD11b+) and T cells (CD4+ and CD8+). Furthermore, we demonstrated, for the first time, that this Blimp-1 promoter fragment also drives EGFP expression in erythroid lineage (Ter119+) and embryonic livers. Finally, EGFP was expressed in the testes of transgenic mice in a cell-specific manner with expression weakly in primary spermatocytes and strongly in spermatids, but not in spermatogonia or spermatozoa. Our studies collectively suggest that Blimp-1 may play a general role in the development of hematopoietic lineages and a stage-specific role in spermatogenesis.

摘要

B淋巴细胞诱导成熟蛋白-1(Blimp-1)是一种参与B细胞终末分化的转录抑制因子。最近的研究表明,它在髓系细胞和T细胞的分化中也发挥作用。通过报告基因分析,我们发现4.4 kb、2.5 kb和1.6 kb的小鼠Blimp-1启动子构建体在体外具有相似的转录活性。为了研究Blimp-1启动子在体内的功能,我们构建了一个小鼠转基因品系,其中EGFP的表达由4.4 kb的Blimp-1启动子片段驱动。在多个造血谱系中检测到EGFP表达,包括造血祖细胞(c-kit+)、不同发育阶段的B细胞(B220+、IgM+、IgD+和CD138+)、髓系细胞(Gr1+和CD11b+)以及T细胞(CD4+和CD8+)。此外,我们首次证明,这个Blimp-1启动子片段也能驱动EGFP在红系谱系(Ter119+)和胚胎肝脏中表达。最后,EGFP在转基因小鼠的睾丸中以细胞特异性方式表达,在初级精母细胞中表达较弱,在精子细胞中表达较强,但在精原细胞或精子中不表达。我们的研究共同表明,Blimp-1可能在造血谱系发育中发挥普遍作用,在精子发生中发挥阶段特异性作用。

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