title: Guwiyang Wurra--'Fire Mouse': a global gene knockout model for TSPO/PBR drug development, loss-of-function and mechanisms of compensation studies.
abstract: The highly conserved 18-kDa translocator protein (TSPO) or peripheral benzodiazepine receptor (PBR), is being investigated as a diagnostic and therapeutic target for disease conditions ranging from inflammation to neurodegeneration and behavioural illnesses. Many functions have been attributed to TSPO/PBR including a role in the mitochondrial permeability transition pore (MPTP), steroidogenesis and energy metabolism. In this review, we detail the recent developments in determining the physiological role of TSPO/PBR, specifically based on data obtained from the recently generated Tspo knockout mouse models. In addition to defining the role of TSPO/PBR, we also describe the value of Tspo knockout mice in determining the selectivity, specificity and presence of any off-target effects of TSPO/PBR ligands.
authors.affiliation: Life Sciences, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ryan.middleton@ansto.gov.au.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Middleton
authors.affiliation: Life Sciences, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia National Imaging Facility, Brain and Mind Research Institute and Faculty of Health Sciences, University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Liu
authors.affiliation: Life Sciences, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia National Imaging Facility, Brain and Mind Research Institute and Faculty of Health Sciences, University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Banati
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004734:Energy Metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics* / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*
chemical_list: C504993:6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo(1,2-a)pyridine-3-acetamide; D019086:Bridged Bicyclo Compounds, Heterocyclic; C463819:Bzrp protein, mouse; D007546:Isoquinolines; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018079:Receptors, GABA; D013256:Steroids; C037850:PK 11195
keywords: TSPO/PBR; compound development; energy; knockout; metabolism; mitochondria