ArticleBiomedical reports2017
Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1.
Article in Biomedical reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Human brain organoids for understanding substance use disorders.Drug metabolism and pharmacokinetics · 2025Review
- Human IPSC-Derived PreBötC-Like Neurons and Development of an Opiate Overdose and Recovery Model.Advanced biology · 2024Article
- Circular PCR as an efficient and precise umbrella of methods for the generation of circular dsDNA with staggered nicks: Mechanism and types.Biology methods & protocols · 2024Article
- Evidence for Endogenous Opioid Dependence Related to Latent Sensitization in a Rat Model of Chronic Inflammatory Pain.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The Mu opioid receptor (MOR) mediates various functions of opioid-induced analgesia, euphoria and respiratory depression, and is a major target of opioid analgesics. Understanding of MOR gene expression among species is important for understanding its analgesic function in humans. In the current study, the polypyrimidine/polypurine (PPy/u) region, a key element of MOR gene expression, was compared in humans and mice. The mouse PPy/u element is highly homologous to its human element (84%), and the mouse MOR (mMOR) reporter drives luciferase activity 35-fold more effectively than the human MOR (hMOR) reporter. The structural study of reporter plasmids using S1 nuclease indicates that the mouse PPy/u element has a particular conformational structure, namely a single-stranded DNA (ssDNA) region that promotes strong promoter activity. DNA electrophoretic mobility shift assays demonstrated that the recombinant α-complex protein 1 (α-CP1) is capable of binding to a single-stranded mouse PPy/u sequence. Furthermore, plasmid-expressing α-CP1 activated the expression of a luciferase reporter when cotransfected with a single-stranded (p336/306) construct. In addition, the α-CP1 gene induced the mMOR gene in mouse neuronal cells and did not induce the human neuronal MOR gene. The current study demonstrates that α-CP1 functions as a transcriptional activator in the mMOR gene, but does not function in the hMOR gene due to species-specific structural differences. The differences in human and mouse MOR gene expression are based on α-CP1 and the ssDNA structure of the MOR promoter. The MOR gene is species-specifically regulated, as the PPy/u element adopts a unique species-specific conformation and α-CP1 recruitment.
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Registered trials
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