Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types
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Published:2023-09-13
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Salimando Gregory J., Tremblay SébastienORCID, Kimmey Blake A., Li Jia, Rogers Sophie A., Wojick Jessica A., McCall Nora M., Wooldridge Lisa M., Rodrigues Amrith, Borner Tito, Gardiner Kristin L., Jayakar Selwyn S., Singeç IlyasORCID, Woolf Clifford J.ORCID, Hayes Matthew R.ORCID, De Jonghe Bart C., Bennett F. ChristianORCID, Bennett Mariko L., Blendy Julie A.ORCID, Platt Michael L., Creasy Kate TownsendORCID, Renthal William R., Ramakrishnan CharuORCID, Deisseroth KarlORCID, Corder Gregory
Abstract
AbstractWith concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target and manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools and transgenic models for gaining long-term genetic access to MOR+ neural cell types and circuits involved in modulating pain, analgesia and addiction across species are limited. To address this, we developed a catalog of MOR promoter (MORp) based constructs packaged into adeno-associated viral vectors that drive transgene expression in MOR+ cells. MORp constructs designed from promoter regions upstream of the mouse Oprm1 gene (mMORp) were validated for transduction efficiency and selectivity in endogenous MOR+ neurons in the brain, spinal cord, and periphery of mice, with additional studies revealing robust expression in rats, shrews, and human induced pluripotent stem cell (iPSC)-derived nociceptors. The use of mMORp for in vivo fiber photometry, behavioral chemogenetics, and intersectional genetic strategies is also demonstrated. Lastly, a human designed MORp (hMORp) efficiently transduced macaque cortical OPRM1+ cells. Together, our MORp toolkit provides researchers cell type specific genetic access to target and functionally manipulate mu-opioidergic neurons across a range of vertebrate species and translational models for pain, addiction, and neuropsychiatric disorders.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference114 articles.
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