RGD Reference Report - Complete knockout of the nociceptin/orphanin FQ receptor in the rat does not induce compensatory changes in mu, delta and kappa opioid receptors. - Rat Genome Database

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Complete knockout of the nociceptin/orphanin FQ receptor in the rat does not induce compensatory changes in mu, delta and kappa opioid receptors.

Authors: Homberg, J R  Mul, J D  de Wit, E  Cuppen, E 
Citation: Homberg JR, etal., Neuroscience. 2009 Sep 29;163(1):308-15. doi: 10.1016/j.neuroscience.2009.06.021. Epub 2009 Jun 12.
RGD ID: 13792569
Pubmed: PMID:19527777   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2009.06.021   (Journal Full-text)

The nociceptin/orphanin FQ (N/OFQ) opioid peptide receptor (NOPr) is a new member of the opioid receptor family consisting of mu, delta and kappa opioid receptors. The anti-opioid properties of its endogenous ligand, N/OFQ provide the receptor interesting potentials in symptoms and processes related to drug addiction, learning and memory, anxiety and depression, and nociception. Using target-selected N-ethyl-N-nitrosourea (ENU)-driven mutagenesis we recently generated a rat model bearing a premature stop codon in the opioid-like receptor (oprl1) gene, and here we describe the primary characterization of this novel model. Data revealed that [(3)H]N/OFQ binding to brain slices was completely absent in rats homozygous for the premature stop codon (oprl1(-/-)). Heterozygous rats displayed an intermediate level of NOPr binding. Oprl1 receptor transcript levels, as determined by Northern blot analysis, were reduced by approximately 50% in oprl1(-/-) rats compared to wild-type controls (oprl1(+/+)), and no alternative spliced transcripts were observed. Quantitative autoradiographic mapping of mu, delta and kappa opioid receptors using [(3)H]DAMGO, [(3)H]deltorphin and [(3)H]CI-977, respectively, did not show any changes in opioid receptor binding. In conclusion, we present a novel mutant rat lacking NOPr without compensatory changes in mu, delta and kappa opioid receptors. We anticipate that this mutant rat will have heuristic value to further understand the function of NOPr.



Objects referenced in this article
Gene Oprl1m1Hubr opioid related nociceptin receptor 1; ENU induced mutant1, Hubr Rattus norvegicus
Strain WI-Oprl1m1Hubr+/- null Rattus norvegicus
Strain WI-Oprl1m1Hubr-/- NOPr knockout rat Rattus norvegicus

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