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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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Abstract

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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Acknowledgments

The authors would like to acknowledge Dr. Louis Dettin for his assistance and Dr. Laurent Lecanu for help with the brain data analysis. This work was supported by grants from the National Institutes of Health (R01 ES07747) and the Canadian Institutes of Health Research (MOP 102647) to V.P. V.P. was also supported by a Canada Research Chair in Biochemical Pharmacology. The Research Institute of the MUHC was supported by a center grant from Le Fonds de la recherche du Québec – Santé.

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Correspondence to Vassilios Papadopoulos.

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Wang, HJ., Fan, J. & Papadopoulos, V. Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription. Cell Tissue Res 350, 261–275 (2012). https://doi.org/10.1007/s00441-012-1478-5

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  • DOI: https://doi.org/10.1007/s00441-012-1478-5

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