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HumanFGF1promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice

机译:HumanFGF1promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFp transgenic mice

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摘要

FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease.
机译:FGF1参与多种生物学功能,并在神经保护作用中发挥重要作用。我们以前的研究表明,在人脑和视网膜中,FGF1B启动子控制FGF1的表达。但是,尚不清楚FGF1在大脑中的确切功能和调控。在这里,我们生成了在人FGF1B启动子(-540至+31)控制下表达GFP报告基因的F1B-GFP转基因小鼠。使用F1B-GFP转基因小鼠的新鲜大脑切片,我们发现F1B-GFP细胞在整个大脑的心室系统中表达强荧光信号。免疫组织化学的结果进一步表明,F1B-GFP转基因小鼠的大脑中存在两个不同的F1B-GFP(+)细胞群体。我们证明了F1B-GFP(+)细胞的一个群体是室管膜细胞,其分布在整个心室,而F1B-GFP(+)细胞的第二个群体是神经元细胞,它们将长过程投射到特定区域的多个方向的大脑。 F1B-GFP(+)细胞和酪氨酸羟化酶的双重标记表明F1B-GFP(+)-神经元细胞的亚群是多巴胺能神经元。重要的是,这些F1B-GFP(+)/ TH(+)细胞分布在主要的多巴胺能神经元组中,包括下丘脑,腹侧被盖区和沟缝核。这些结果表明,人FGF1B启动子在室管膜细胞,神经元和一部分多巴胺能神经元中具有活性。因此,F1B-GFP转基因小鼠不仅为研究FGF1基因在体内的表达提供了动物模型,而且为了解FGF1在帕金森氏病和阿尔茨海默氏病等神经退行性疾病中的作用提供了动物模型。

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