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.

Minireview: Translocator Protein (TSPO) and Steroidogenesis: A Reappraisal

“…Both human and mouse Tspo genes translate to a 169 amino acid protein with 81% sequence homology (19,20). Expression of TSPO has been reported in different tissues including heart, brain, lung, spleen, testis, ovary, adrenal, kidney, bone marrow, salivary gland, adipose tissue, skin and liver (21)(22)(23); and within these tissues, TSPO expression is regional and/or cell type specific (24).…”

Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

“…The first step consists in the transportation of the common precursor, cholesterol, from the outer to the inner mitochondrial membrane as a result of the activity of the steroidogenic acute regulatory protein (StAR) and the translocator protein of 18 kDa (TSPO); both proteins are widely expressed in the CNS (Lavaque et al, 2006;Sierra et al, 2003;Wang et al, 2012).…”

Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research

“…The translocator protein (TSPO) is a five transmembrane structure located at the outer and inner mitochondrial membrane contact sites, expression of which is enriched in steroidogenic organs (103). Activation of TSPO by synthetic TSPO ligands elicits pleiotropic neuroprotective and cognitive benefits, mechanistically linked to regulation of mitochondrial function, including the facilitation of mitochondrial cholesterol import for steroidogenesis (104).…”