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基因改造不影响巢蛋白启动子-GFP转基因小鼠中神经干细胞的干性。

Genetic modification does not affect the stemness of neural stem cells in nestin promoter-GFP transgenic mice.

作者信息

Park Jae Hyun, Ahn Joon Ik, Kim So Young, Park Ki Sook, Lee Young Don, Yamaguchi Masahiro, Chung Hye Joo

机构信息

Department of Pharmacology, National Institute of Toxicological Research, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-704, Republic of Korea.

出版信息

Neurosci Lett. 2007 Jun 29;421(3):185-90. doi: 10.1016/j.neulet.2007.02.069. Epub 2007 Mar 2.

Abstract

Because nestin promoter-GFP mice have frequently been used in neural stem cell (NSC) research, it is essential to prove that there is no alteration in the stemness of NSCs derived from this transgenic model for the interpretation and validity of the data. We compared the stemness of NSCs derived from transgenic mice expressing GFP driven by the nestin enhancer with those from wild-type (C57BL/6) mice with respect to the general gene expression profile, expression of neural stem cell markers as nestin and Sox2, and responsiveness to neurotrophins (BDNF, PDGF-BB, and NT-3). The gene expression profile analysis showed that the coefficient of correlation between the two groups was very high (r=0.9865) in the total genes. We found that 23 genes were either up- or down-regulated more than two-fold in the NSCs from the transgenic mice (p<0.05), without any obvious functional relatedness among them. Likewise, there was no difference between the two mouse groups in the expression of nestin or Sox2, the ability to form neurospheres and the neuronal differentiation of NSCs by neurotrophins. Taken together, the self-renewal and neuronal differentiation ability of NSCs from the transgenic mice showed the great similarity to those from wild-type mice. Such information will be useful when the properties of NSCs are evaluated following genetic modification in such a nestin-GFP Tg model.

摘要

由于巢蛋白启动子 - 绿色荧光蛋白(GFP)小鼠经常被用于神经干细胞(NSC)研究,为了数据的解释和有效性,证明源自这种转基因模型的神经干细胞干性没有改变至关重要。我们比较了由巢蛋白增强子驱动表达GFP的转基因小鼠来源的神经干细胞与野生型(C57BL / 6)小鼠来源的神经干细胞在一般基因表达谱、神经干细胞标志物如巢蛋白和Sox2的表达以及对神经营养因子(BDNF、PDGF - BB和NT - 3)的反应性方面的干性。基因表达谱分析表明,两组在全部基因中的相关系数非常高(r = 0.9865)。我们发现转基因小鼠来源的神经干细胞中有23个基因上调或下调超过两倍(p < 0.05),它们之间没有明显的功能相关性。同样,两组小鼠在巢蛋白或Sox2的表达、形成神经球的能力以及神经营养因子诱导神经干细胞的神经元分化方面没有差异。综上所述,转基因小鼠来源的神经干细胞的自我更新和神经元分化能力与野生型小鼠来源的神经干细胞非常相似。当在这种巢蛋白 - GFP转基因模型中进行基因修饰后评估神经干细胞的特性时,这些信息将很有用。

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