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A novel Oprm1-Cre mouse maintains endogenous expression, function and enables detailed molecular characterization of μ-opioid receptor cells
Mengaziol, Juliet Dunn, Amelia D. Salimando, Gregory Wooldridge, Lisa Crues-Muncunill, Jordi Eacret, Darrell Bland, Kathryn Ehrlich, Michelle E.
Mengaziol, Juliet
Dunn, Amelia D.
Salimando, Gregory
Wooldridge, Lisa
Crues-Muncunill, Jordi
Eacret, Darrell
Bland, Kathryn
Ehrlich, Michelle E.
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Journal article
Date
2022-12-19
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Neural Sciences
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http://dx.doi.org/10.1371/journal.pone.0270317
Abstract
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.
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Citation
Mengaziol J, Dunn AD, Salimando G, Wooldridge L, Crues-Muncunill J, Eacret D, et al. (2022) A novel Oprm1-Cre mouse maintains endogenous expression, function and enables detailed molecular characterization of μ-opioid receptor cells. PLoS ONE 17(12): e0270317. https://doi.org/10.1371/journal.pone.0270317
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PLoS ONE, Vol. 17
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