A novel Oprm1-Cre mouse maintains endogenous expression, function and enables detailed molecular characterization of μ-opioid receptor cells.

Autor: Mengaziol J; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Dunn AD; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Salimando G; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Wooldridge L; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Crues-Muncunill J; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America., Eacret D; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Chen C; Center for Substance Abuse Research and Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America., Bland K; Center for Substance Abuse Research and Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America., Liu-Chen LY; Center for Substance Abuse Research and Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America., Ehrlich ME; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America., Corder G; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Blendy JA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Dec 19; Vol. 17 (12), pp. e0270317. Date of Electronic Publication: 2022 Dec 19 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0270317
Abstrakt: Key targets of both the therapeutic and abused properties of opioids are μ-opioid receptors (MORs). Despite years of research investigating the biochemistry and signal transduction pathways associated with MOR activation, we do not fully understand the cellular mechanisms underlying opioid addiction. Given that addictive opioids such as morphine, oxycodone, heroin, and fentanyl all activate MORs, and current therapies such as naloxone and buprenorphine block this activation, the availability of tools to mechanistically investigate opioid-mediated cellular and behavioral phenotypes are necessary. Therefore, we derived, validated, and applied a novel MOR-specific Cre mouse line, inserting a T2A cleavable peptide sequence and the Cre coding sequence into the MOR 3'UTR. Importantly, this line shows specificity and fidelity of MOR expression throughout the brain and with respect to function, there were no differences in behavioral responses to morphine when compared to wild type mice, nor are there any alterations in Oprm1 gene expression or receptor density. To assess Cre recombinase activity, MOR-Cre mice were crossed with the floxed GFP-reporters, RosaLSLSun1-sfGFP or RosaLSL-GFP-L10a. The latter allowed for cell type specific RNA sequencing via TRAP (Translating Ribosome Affinity Purification) of striatal MOR+ neurons following opioid withdrawal. The breadth of utility of this new tool will greatly facilitate the study of opioid biology under varying conditions.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2022 Mengaziol et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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