title: Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription.
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.
authors.affiliation: The Research Institute of the McGill University Health Center, McGill University, Montréal, Québec, H3A 1A4, Canada.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Wang
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Fan
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018079:Receptors, GABA / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C463819:Bzrp protein, mouse; D012333:RNA, Messenger; D018079:Receptors, GABA; D049452:Green Fluorescent Proteins