Quantitative trait loci influencing morphine antinociception in four mapping populations

Susan E. Bergeson, Melinda L. Helms, Laurie A. O'Toole, Mark W. Jarvis, Heather S. Hain, Jeffrey S. Mogil, John Belknap

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Abstract

Analgesia (pain reduction, or antinociception) is a classical and clinically important effect of morphine administration, and in rodent models sensitivity to morphine has been shown to be strongly influenced by genotype. For example, several studies have reported marked differences in morphine antinociception between the insensitive C57BL/6 (B6) and sensitive DBA/2 (D2) inbred mouse strains on the hot-plate assay. This prompted the present genome-wide search for quantitative trait loci (QTLs) that are chromosomal sites influencing the magnitude of antinociception, by using four mapping populations derived from the B6 and D2 progenitor inbred strains. These four were the BXD recombinant inbred (RI) strain set, an F2 (B6D2F2) population, short-term selective breeding for antinociception from a B6D2F2 founding population, and incipient or completed congenic strains. In the BXD RI set and in the B6D2F2, a genome-wide search identified 10-12 provisional QTLs at a nominal p <.05. The other populations were subsequently used as confirmation steps to test each of the provisional QTL regions. Based on all available mapping populations, four QTLs emerged as significant (p <.00005) on proximal Chromosome (Chr) 1 (females only), proximal Chr 9 (females only), mid Chr 9, and proximal Chr 10. The Chr 10 QTL comaps to the same region as the μ-opioid receptor gene (Oprm); this receptor is a known mediator of morphine's antinociceptive effects. The Chr 1 QTL was evident only in females and comapped with the κ-opioid receptor gene, Oprk.

Original languageEnglish (US)
Pages (from-to)546-553
Number of pages8
JournalMammalian Genome
Volume12
Issue number7
DOIs
StatePublished - 2001

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Quantitative Trait Loci
Morphine
Population
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 1
Opioid Receptors
Genome
Inbred Strains Mice
Exercise Test
Analgesia
Genes
Rodentia
Genotype
Pain

ASJC Scopus subject areas

  • Genetics

Cite this

Bergeson, S. E., Helms, M. L., O'Toole, L. A., Jarvis, M. W., Hain, H. S., Mogil, J. S., & Belknap, J. (2001). Quantitative trait loci influencing morphine antinociception in four mapping populations. Mammalian Genome, 12(7), 546-553. https://doi.org/10.1007/s003350020022

Quantitative trait loci influencing morphine antinociception in four mapping populations. / Bergeson, Susan E.; Helms, Melinda L.; O'Toole, Laurie A.; Jarvis, Mark W.; Hain, Heather S.; Mogil, Jeffrey S.; Belknap, John.

In: Mammalian Genome, Vol. 12, No. 7, 2001, p. 546-553.

Research output: Contribution to journalArticle

Bergeson, SE, Helms, ML, O'Toole, LA, Jarvis, MW, Hain, HS, Mogil, JS & Belknap, J 2001, 'Quantitative trait loci influencing morphine antinociception in four mapping populations', Mammalian Genome, vol. 12, no. 7, pp. 546-553. https://doi.org/10.1007/s003350020022
Bergeson SE, Helms ML, O'Toole LA, Jarvis MW, Hain HS, Mogil JS et al. Quantitative trait loci influencing morphine antinociception in four mapping populations. Mammalian Genome. 2001;12(7):546-553. https://doi.org/10.1007/s003350020022
Bergeson, Susan E. ; Helms, Melinda L. ; O'Toole, Laurie A. ; Jarvis, Mark W. ; Hain, Heather S. ; Mogil, Jeffrey S. ; Belknap, John. / Quantitative trait loci influencing morphine antinociception in four mapping populations. In: Mammalian Genome. 2001 ; Vol. 12, No. 7. pp. 546-553.
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