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Please use this identifier to cite or link to this item: http://apo.ansto.gov.au/dspace/handle/10238/8979

Title: Positron emission tomography and functional characterization of a complete PBR/TSPO knockout
Authors: Banati, RB
Middleton, RJ
Chan, R
Hatty, CR
Wai-Yong Kam, W
Qinn, C
Graeber, MB
Parmar, A
Callaghan, P
Fok, S
Howell, NR
Gregoire, M
Szabo, A
Pham, T
Liu, GJ
Keywords: Positron computed tomography
Porteins
Metabolism
Protoporphyrins
Membrane proteins
Anti-inflammatory agents
Issue Date: 19-Nov-2014
Publisher: Springer Nature
Citation: Banati, R. B., Middleton, R. J., Chan, R., Hatty, C. R., Wai-Ying Kam, W., Quin, C.,Graeber, M. B., Parmar, A., Callaghan, P., Fok, S., Howell, N., Gregoire, M., SSzabo, A., Pham, T., Davis, E., Liu, G.-J. (2014). Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nature Communications, 5, 5452. doi:10.1038/ncomms6452
Abstract: The evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer’s disease to anxiety. Here we show that global C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from GuwiyangWurraTSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of GuwiyangWurraTSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs. © 2014 Macmillan Publishers Limited. All rights reserved.
URI: https://www.nature.com/articles/ncomms6452
http://apo.ansto.gov.au/dspace/handle/10238/8979
ISSN: 2041-1723
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