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小鼠GATA - 3基因的胚胎表达与克隆

Embryonic expression and cloning of the murine GATA-3 gene.

作者信息

George K M, Leonard M W, Roth M E, Lieuw K H, Kioussis D, Grosveld F, Engel J D

机构信息

Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Il 60208-3500.

出版信息

Development. 1994 Sep;120(9):2673-86. doi: 10.1242/dev.120.9.2673.

Abstract

We describe the embryonic expression pattern as well as the cloning and initial transcriptional regulatory analysis of the murine (m) GATA-3 gene. In situ hybridization shows that mGATA-3 mRNA accumulation is temporally and spatially regulated during early development: although found most abundantly in the placenta prior to 10 days of embryogenesis, mGATA-3 expression becomes restricted to specific cells within the embryonic central nervous system (in the mesencephalon, diencephalon, pons and inner ear) later in gestation. GATA-3 also shows a restricted expression pattern in the peripheral nervous system, including terminally differentiating cells in the cranial and sympathetic ganglia. In addition to this distinct pattern in the nervous system, mGATA-3 is also expressed in the embryonic kidney and the thymic rudiment, and further analysis showed that it is expressed throughout T lymphocyte differentiation. To begin to investigate how this complex gene expression pattern is elicited, cloning and transcriptional regulatory analyses of the mGATA-3 gene were initiated. At least two regulatory elements (one positive and one negative) appear to be required for appropriate tissue-restricted regulation after transfection of mGATA-3-directed reporter genes into cells that naturally express GATA-3 (T lymphocytes and neuroblastoma cells). Furthermore, this same region of the locus confers developmentally appropriate expression in transgenic mice, but only in a subset of the tissues that naturally express the gene.

摘要

我们描述了小鼠(m)GATA-3基因的胚胎表达模式以及克隆和初步转录调控分析。原位杂交显示,mGATA-3 mRNA的积累在早期发育过程中受到时间和空间的调控:尽管在胚胎发生10天之前在胎盘中含量最为丰富,但在妊娠后期,mGATA-3的表达局限于胚胎中枢神经系统内的特定细胞(中脑、间脑、脑桥和内耳)。GATA-3在周围神经系统中也呈现出受限的表达模式,包括颅神经节和交感神经节中终末分化的细胞。除了在神经系统中的这种独特模式外,mGATA-3在胚胎肾脏和胸腺原基中也有表达,进一步分析表明它在整个T淋巴细胞分化过程中都有表达。为了开始研究这种复杂的基因表达模式是如何产生的,我们启动了mGATA-3基因的克隆和转录调控分析。将mGATA-3指导的报告基因转染到天然表达GATA-3的细胞(T淋巴细胞和成神经细胞瘤细胞)中后,至少两个调控元件(一个正向和一个负向)似乎是适当的组织限制性调控所必需的。此外,该基因座中的相同区域在转基因小鼠中赋予了发育上适当的表达,但仅在天然表达该基因的组织的一个子集中表达。

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