Murine Chromosomal Location of the μ and κ Opioid Receptor Genes

Kozak, Christine A.; Filie, Jane D.; Adamson, M. C.; Chen, Yan; Yu, Lei

doi:10.1006/geno.1994.1331

Cited by 53 publications

(25 citation statements)

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“…This QTL for oral morphine preference, termed Mop2, was confirmed in a follow-up study (Alexander et al, 1996) and support was generated for the concept that it had a broader influence with regard to the pharmacological effects of morphine being involved also in determining morphine-induced analgesia and the density of [ 3 H]naloxone binding sites in the brain (Belknap et al, 1995). Subsequent mapping of the Mu opioid receptor gene (Oprm) to the same chromosomal location as the Mop2 QTL (Kozak et al, 1994;Giros et al, 1995) focused attention on this gene as a strong candidate for mediating differences in opioid-related effects between B6 and D2 mice. In spite of intensive study, the causative genetic variation that underlies Mop2 has yet to be identified.…”

Section: Discussionmentioning

confidence: 84%

“…Quantitative trait locus (QTL) mapping studies indicate that a locus on the proximal end of chromosome 10 called Mop2 harbors a gene(s) that determines a large part of the difference in voluntary oral morphine consumption between B6 and DBA/2 (D2) mice (Berrettini et al, 1994b). The gene encoding the Mu opioid receptor (Oprm) is located on proximal chromosome 10 (Kozak et al, 1994;Giros et al, 1995) and is a compelling candidate for the Mop2 QTL; however, the causative genetic variation between B6 and D2 mice has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Ferraro

Golden

Smith

et al. 2004

Neuropsychopharmacol

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C57BL/6 (B6) and DBA/2 (D2) mice exhibit disparate behavior when tested for voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice consuming 10 times more drug than D2 mice. Previous genetic mapping studies identified a locus, Mop2, on the proximal part of chromosome 10 that explained over half of the genetic variance in this mouse model of opioid selfadministration. We constructed a set of reciprocal congenic strains between B6 and D2 mice in which the proximal portion of chromosome 10 has been introgressed from one strain onto the background of the other. We tested mice from this pair of reciprocal strains together with progenitor B6 and D2 mice in a two-bottle choice drinking paradigm with morphine and quinine. The results showed that introgression of chromosome 10 alleles from the B6 strain onto a D2 genetic background increased voluntary morphine intake four-fold compared to progenitor D2 mice. Preference for morphine was also increased significantly in D2.B6-Mop2 mice compared to progenitor D2 mice. Conversely, introgression of chromosome 10 alleles from the D2 strain onto a B6 genetic background decreased morphine intake by half compared to progenitor B6 mice in B6.D2 -Mop2 mice; however, high morphine preference was maintained in this congenic strain most likely due to strong quinine aversion. When quinine was eliminated from the control bottle, morphine preference in B6.D2-Mop2 mice was decreased significantly relative to B6 and D2.B6-Mop2 mice. Overall, these data confirm the existence of a gene(s) on chromosome 10 proximal to D10Mit124 that has a strong influence on the difference in morphine drinking behavior between B6 and D2 mice.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Ferraro

Golden

Smith

et al. 2004

Neuropsychopharmacol

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“…The MOR gene (Oprm1) spans approximately 250 kb of proximal Chr. 10 (Kozak et al, 1994;Giros et al, 1995) and contains at least 19 alternatively spliced exons (Doyle et al, 2007a, b) that encode a number of MOR isoforms capable of binding morphine, other opiates, and endogenous opioid peptides (Pan et al, , 2000(Pan et al, , 2001Bolan et al, 2004). There is ample pharmacological evidence that MORs represent the major sites of interaction of clinically used opioid analgesics, particularly morphine (Pasternak, 2001a).…”

Section: Discussionmentioning

confidence: 99%

Fine Mapping of a Major QTL Influencing Morphine Preference in C57BL/6 and DBA/2 Mice Using Congenic Strains

Doyle

Furlong

Schwebel

et al. 2008

Neuropsychopharmacol

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C57BL/6J (B6) and DBA/2J (D2) mice differ in behaviors related to substance abuse, including voluntary morphine consumption and preference in a two-bottle choice paradigm. Two major quantitative trait loci (QTL) for morphine consumption and preference exist between these strains on chromosomes (Chrs.) 6 and 10 when the two-bottle choice involves morphine in saccharin vs quinine in saccharin. Here, we report the refinement of the Chr. 10 QTL in subcongenic strains of D2.B6-Mop2 congenic mice described previously. With these subcongenic mouse strains, we have divided the introgressed region of Chr. 10 containing the QTL gene(s) into two segments, one between the acromere and Stxbp5 (in D2.B6-Mop2-P1 mice) and the other between marker D10Mit211 and marker D10Mit51 (in D2.B6-Mop2-D1 mice). We find that, similar to B6 mice, the D2.B6-Mop2-P1 congenic mice exhibit a strong preference for morphine over quinine, whereas D2.B6-Mop2-D1 congenic mice avoid morphine (similar to D2 mice). We have also created a line of double congenic mice, B6.D2-Mop2.Qui, which contains both Chr. 10 and Chr. 6 QTL. We find that they are intermediate in their morphine preference scores when compared with B6 and D2 animals. Overall, these data suggest that the gene(s) involved in morphine preference in the morphine-quinine two-bottle choice paradigm are contained within the proximal region of Chr. 10 (which harbors Oprm1) between the acromere and Stxbp5, as well as on distal Chr. 6 between marker D6Mit10 and the telomere.

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“…Studies of quantitative trait loci in mice identified a chromosomal region containing the opioid receptor gene as contributing to a substantial amount of the variance in analgesic and reward responses to morphine (Belknap and Crabbe, 1992;Berrettini et al, 1994;Kozak et al, 1994;Belknap et al, 1995;Crabbe et al, 1999). Also, studies of mice with targeted deletion of the opioid receptor gene definitively established this receptor as essential for morphine analgesia, physical dependence, and reward as measured by antinociception, withdrawal, conditioned place preference, and self-administration studies (Matthes et al, 1996;Sora et al, 1997;Kitanaka et al, 1998;Loh et al, 1998;Becker et al, 2000).…”

Section: Selected Identified Genesmentioning

confidence: 99%

Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments

et al. 2005

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Murine Chromosomal Location of the μ and κ Opioid Receptor Genes

Cited by 53 publications

References 0 publications

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Fine Mapping of a Major QTL Influencing Morphine Preference in C57BL/6 and DBA/2 Mice Using Congenic Strains

Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments

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