Fine mapping of a major quantitative trait locus mediating multiple opioid addiction behaviors
MetadataShow full item record
Opioid addiction is a growing epidemic with no known genetic basis. Mice represent a valuable tool that can be used to better understand the genetic components of opioid addiction by studying opioid induced behaviors such as locomotor activity. The two closely related C57BL/6 substrains, C57BL/6J (B6J) and C57BL/6NJ (B6NJ), exhibit limited genetic diversity, yet display phenotypic differences when under the influence of oxycodone. Quantitative trait locus (QTL) mapping, a discovery based approach to identifying genomic regions underlying statistical variation in complex traits, was used to identify a locus on distal chromosome 1 for oxycodone-induced locomotor activity and withdrawal. F2 offspring from a cross utilizing these substrains that are homozygous B6J across the chromosome 1 QTL compared to offspring that are heterozygous display the same phenotypic differences as the parental strains, namely oxycodone-induced locomotor activity. F2 mice were selected based on distal chromosome 1 genotypes and backcrossed to parental strain C57BL/6J to fine map the QTL interval. Through family analysis, regions proximal to 167 Mb and distal to 187 Mb have been ruled out as containing the QTL mediating oxycodone-induced locomotor activity. Future studies should employ this same technique to fine map the QTL mediating oxycodone withdrawal in order to differentiate whether it is one locus or two loci controlling these oxycodone induced behaviors.