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

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TspoRatcholesterol homeostasis  IMP  RGD 
TspoRatnegative regulation of corticosterone secretion  IMP  RGD 
TspoRatresponse to acetylcholine  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View
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