Günzburg W H, Salmons B, Zimmermann B, Müller M, Erfle V, Brem G
Abteilung für Molekulare Zellpathologie, GSF-Munich, Neuherberg, Germany.
Mol Endocrinol. 1991 Jan;5(1):123-33. doi: 10.1210/mend-5-1-123.
The whey acidic protein (WAP) promoter has been previously used to target the expression of heterologous genes to the mammary glands of transgenic mice. To direct the expression of human GH (hGH) to mouse mammary glands, hGH-coding sequences have been coupled to WAP promoter sequences (WAP-hGH). Female transgenic mice carrying the WAP-hGH constructs show expression of hGH in the mammary gland, demonstrating the functionality of the transgenes. However, when other organs from these transgenic mice were examined, high level expression of hGH was unexpectedly observed in the brains of all male and female mice. Using in situ hybridization or immunohistochemistry, hGH expression from the transgene was seen to occur specifically in Bergman glia cells. In contrast, mice carrying hGH-coding sequences linked to the metallothionein promoter do not express hGH in these cells. Neither the endogenous WAP gene nor at least three other transgenes in which heterologous genes have been placed under the transcriptional control of the WAP promoter are expressed in the brain. Thus, we propose that the combination of the WAP promoter and the hGH structural gene results in a novel tissue specificity in the Bergman glia.
乳清酸性蛋白(WAP)启动子此前已被用于将异源基因的表达靶向到转基因小鼠的乳腺。为了将人生长激素(hGH)的表达导向小鼠乳腺,已将hGH编码序列与WAP启动子序列(WAP-hGH)连接。携带WAP-hGH构建体的雌性转基因小鼠在乳腺中显示出hGH的表达,证明了转基因的功能。然而,当检查这些转基因小鼠的其他器官时,在所有雄性和雌性小鼠的大脑中意外地观察到了hGH的高水平表达。使用原位杂交或免疫组织化学方法,发现转基因的hGH表达特异性地发生在伯格曼胶质细胞中。相比之下,携带与金属硫蛋白启动子连接的hGH编码序列的小鼠在这些细胞中不表达hGH。内源性WAP基因以及至少其他三个已将异源基因置于WAP启动子转录控制之下的转基因在大脑中均不表达。因此,我们提出WAP启动子和hGH结构基因的组合导致了伯格曼胶质细胞中一种新的组织特异性。