Identification and functional significance of polymorphisms in the mu-opioid receptor gene (Oprm) promoter of C57BL/6 and DBA/2 mice

Neuroscience Research
Glenn A DoyleRussell J Buono

Abstract

C57BL/6J and DBA/2J mice demonstrate differences in morphine preference when tested in a two-bottle choice paradigm. Quantitative trait loci (QTL) mapping suggested the proximal region of chromosome 10 was responsible for 41% of the observed genetic variance. The mu-opioid receptor (MOR) gene (Oprm) maps to this region and is a prime candidate for explaining the QTL. We hypothesized that variations in Oprm between these strains are responsible for differences in morphine preference. We identify five single nucleotide polymorphisms (SNPs) in the Oprm promoter; three within or near putative transcription factor binding sites. Promoter fragments were amplified from genomic DNA by polymerase chain reaction (PCR) and subcloned into luciferase reporter vectors. A significant difference in basal Oprm promoter activity was seen with C57BL/6 and DBA/2 approximately 1675 constructs in MOR-positive BE(2)-C cells, but not in MOR-negative Neuro-2a cells. In BE(2)-C cells, average DBA/2 approximately 1675 construct activity was 1.3-2.0x greater than average C57BL/6 activity suggesting that the SNPs might alter MOR expression in these two mouse strains. Significant differences in promoter activities between the two cell lines suggest that cel...Continue Reading

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Citations

Apr 30, 2013·Neuropharmacology·Gavril W Pasternak
Feb 22, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Glenn A DoyleThomas N Ferraro
Apr 24, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jenica D TapocikNorman H Lee
Aug 25, 2007·Cerebral Cortex·Takuya NittaKikuro Fukushima
Nov 14, 2012·Addiction Biology·Emily C Eastwood, Tamara J Phillips

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