Galou M, Pournin S, Ensergueix D, Ridet J L, Tchélingérian J L, Lossouarn L, Privat A, Babinet C, Dupouey P
Unité de Biochimie des Antigènes, Institut Pasteur, Paris, France.
Glia. 1994 Dec;12(4):281-93. doi: 10.1002/glia.440120405.
The expression of the glial fibrillary acidic protein (GFAP), a component of astroglial intermediate filaments, is regulated under developmental and pathological conditions. In order to characterize DNA sequences involved in such regulations, we produced transgenic mice bearing 2 kb of the 5' flanking region of the murine GFAP gene linked to the Escherichia coli beta-galactosidase (beta-gal) reporter gene. Seven transgenic lines were obtained. We observed that the regulatory elements present in the transgene GFAP-nls-LacZ direct an expression in the neural and non-neural tissue and target in vivo an unexpected subpopulation of astrocyte. In the developing brain, beta-gal activity and GFAP appeared simultaneously and in the same region, on embryonic day 18 (E18), suggesting that the 2 kb of the promoter contains the regulatory sequences responsible for the perinatal vimentin/GFAP switch. In addition, we demonstrated that the 2 kb sequence of the GFAP promoter used in the transgene possess elements which are activated after a surgical injury, thus permitting to study some aspects of reactive gliosis in these transgenic mice. These transgenic lines provide a useful tool by enabling further studies of astroglial and, probably, neuronal physiologies.
胶质纤维酸性蛋白（GFAP）是星形胶质细胞中间丝的一个组成部分，其表达在发育和病理条件下受到调控。为了鉴定参与此类调控的DNA序列，我们构建了转基因小鼠，其携带与大肠杆菌β-半乳糖苷酶（β-gal）报告基因相连的鼠源GFAP基因5'侧翼区的2 kb片段。获得了7个转基因品系。我们观察到转基因GFAP-nls-LacZ中存在的调控元件在神经组织和非神经组织中均有表达，并且在体内靶向一个意外的星形胶质细胞亚群。在发育中的大脑中，β-gal活性和GFAP在胚胎第18天（E18）同时且在同一区域出现，这表明启动子的2 kb片段包含负责围产期波形蛋白/GFAP转换的调控序列。此外，我们证明转基因中使用的GFAP启动子的2 kb序列具有在手术损伤后被激活的元件，从而能够在这些转基因小鼠中研究反应性胶质增生的某些方面。这些转基因品系通过使进一步研究星形胶质细胞以及可能的神经元生理学成为可能，提供了一个有用的工具。
