Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription.
Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription.
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DOI：
10.1007/s00441-012-1478-5
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发表时间：
2012-11
影响因子：
3.6
通讯作者：
Papadopoulos, Vassilios
中科院分区：
文献类型：
--
作者：
Wang, Hui-Jie;Fan, Jinjiang;Papadopoulos, Vassilios
转运蛋白(TransLocator Protein，TSPO)是一种广泛存在的药物和胆固醇结合蛋白，主要存在于线粒体外膜，是线粒体胆固醇转运复合体的一部分。TSPO在类固醇合成和快速增殖的组织中存在较高水平，其生物学作用主要与线粒体功能、类固醇合成和细胞增殖/凋亡有关。TSPO水平的异常与多种疾病有关，包括癌症、内分泌紊乱、脑损伤、神经变性、缺血再灌注损伤和炎症性疾病。在体外和体内对该蛋白功能的研究主要是利用高亲和力的药物配体，如异喹啉羧胺和苯二氮卓，以及最近的基因沉默方法。为了建立体内研究TSPO转录调控的模型，我们建立了TSPO启动子区域控制下的绿色荧光蛋白(GFP)转基因小鼠模型(TSPO-AcGFP)。TSPO-AcGFP、内源性TSPO和TSPO mRNA的表达谱被发现有很好的相关性。TSPO-AcGFP在转基因小鼠的几乎所有组织中都有合成，与野生型小鼠的TSPO一样，TSPO-AcGFP在内分泌和生殖系统的类固醇生成细胞、消化系统上皮细胞、骨骼肌和其他器官中高表达。总之，这种转基因TSPO-AcGFP小鼠模型概括了内源性TSPO的表达模式，可以作为一种有用的、易操作的工具，在活体动物实验中监测TSPO的转录调控和功能。
Translocator protein (TSPO), previously known as the peripheral-type benzodiazepine receptor, is a ubiquitous drug- and cholesterol-binding protein primarily found in the outer mitochondrial membrane as part of a mitochondrial cholesterol transport complex. TSPO is present at higher levels in steroid-synthesizing and rapidly proliferating tissues, and its biological role has been mainly linked to mitochondrial function, steroidogenesis, and cell proliferation/apoptosis. Aberrant TSPO levels have been linked to multiple diseases, including cancer, endocrine disorders, brain injury, neurodegeneration, ischemia-reperfusion injury, and inflammatory diseases. Investigation of the functions of this protein in vitro and in vivo have been mainly carried out using high-affinity drug ligands, such as isoquinoline carboxamides and benzodiazepines, and more recently, gene silencing methods. To establish a model to study the regulation of Tspo transcription in vivo, we generated a transgenic mouse model expressing green fluorescent protein (GFP) from Aequorea coerulescens under control of the Tspo promoter region (Tspo-AcGFP). The expression profiles of Tspo-AcGFP, endogenous TSPO, and Tspo mRNA were found to be well correlated. Tspo-AcGFP synthesis in the transgenic mice was seen in almost every tissue examined, and as with TSPO in wild-type mice, Tspo-AcGFP was highly expressed in steroidogenic cells of the endocrine and reproductive systems, epithelial cells of the digestive system, skeletal muscle, and other organs. In summary, this transgenic Tspo-AcGFP mouse model recapitulates endogenous Tspo expression patterns and could be a useful, tractable tool for monitoring the transcriptional regulation and function of Tspo in live animal experiments.
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影响因子：
4.1
作者：
Batarseh, Amani;Papadopoulos, Vassilios
通讯作者：
Papadopoulos, Vassilios
DOI：
10.1016/0952-0600(90)90044-j
发表时间：
1990-01-01
期刊：
Pulmonary Pharmacology
影响因子：
--
作者：
ADVENIER C;DEVILLIER P;GNASSOUNOU J P
通讯作者：
GNASSOUNOU J P
DOI：
10.1016/0169-328x(86)90004-5
发表时间：
1986-11-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
BASILE, AS;KLEIN, DC;SKOLNICK, P
通讯作者：
SKOLNICK, P
影响因子：
7.3
作者：
CHIOU, LC;CHANG, CC
通讯作者：
CHANG, CC
影响因子：
64.8
作者：
BRAESTRUP, C;ALBRECHTSEN, R;SQUIRES, RF
通讯作者：
SQUIRES, RF