RGD Reference Report - TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis. - Rat Genome Database

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TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis.

Authors: Owen, David R  Fan, Jinjiang  Campioli, Enrico  Venugopal, Sathvika  Midzak, Andrew  Daly, Edward  Harlay, Aline  Issop, Leeyah  Libri, Vincenzo  Kalogiannopoulou, Dimitra  Oliver, Eduardo  Gallego-Colon, Enrique  Colasanti, Alessandro  Huson, Les  Rabiner, Eugenii A  Suppiah, Puvan  Essagian, Charles  Matthews, Paul M  Papadopoulos, Vassilios 
Citation: Owen DR, etal., Biochem J. 2017 Nov 21;474(23):3985-3999. doi: 10.1042/BCJ20170648.
RGD ID: 150429771
Pubmed: PMID:29074640   (View Abstract at PubMed)
PMCID: PMC5697202   (View Article at PubMed Central)
DOI: DOI:10.1042/BCJ20170648   (Journal Full-text)

The 18 kDa translocator protein (TSPO) is a ubiquitous conserved outer mitochondrial membrane protein implicated in numerous cell and tissue functions, including steroid hormone biosynthesis, respiration, cell proliferation, and apoptosis. TSPO binds with high affinity to cholesterol and numerous compounds, is expressed at high levels in steroid-synthesizing tissues, and mediates cholesterol import into mitochondria, which is the rate-limiting step in steroid formation. In humans, the rs6971 polymorphism on the TSPO gene leads to an amino acid substitution in the fifth transmembrane loop of the protein, which is where the cholesterol-binding domain of TSPO is located, and this polymorphism has been associated with anxiety-related disorders. However, recent knockout mouse models have provided inconsistent conclusions of whether TSPO is directly involved in steroid synthesis. In this report, we show that TSPO deletion mutations in rat and its corresponding rs6971 polymorphism in humans alter adrenocorticotropic hormone-induced plasma corticosteroid concentrations. Rat tissues examined show increased cholesteryl ester accumulation, and neurosteroid formation was undetectable in homozygous rats. These results also support a role for TSPO ligands in diseases with steroid-dependent stress and anxiety elements.



Disease Annotations    

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Tspo  (translocator protein)
Tspoem1Vpl  (translocator protein; ZFN induced mutant1, Vpl)
Tspoem2Vpl  (translocator protein; ZFN induced mutant2, Vpl)

Genes (Mus musculus)
Tspo  (translocator protein)

Genes (Homo sapiens)
TSPO  (translocator protein)

Strains
SD-Tspoem1Vpl  (NA)
SD-Tspoem2Vpl  (NA)


Additional Information