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

Ferraro, Thomas N.; Golden, Gregory T.; Smith, George Gilbert; Martin, James F.; Schwebel, Candice L.; Doyle, Glenn A.; Buono, Russell J.; Berrettini, Wade H.

doi:10.1038/sj.npp.1300592

Cited by 36 publications

(71 citation statements)

References 17 publications

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“…The Chr. 10 'Morphine-preference' (Mop) QTL was replicated (Alexander et al, 1996) and has been confirmed in reciprocal congenic mouse strains (Ferraro et al, 2005).…”

Section: Introductionmentioning

confidence: 91%

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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“…The Chr. 10 'Morphine-preference' (Mop) QTL was replicated (Alexander et al, 1996) and has been confirmed in reciprocal congenic mouse strains (Ferraro et al, 2005).…”

Section: Introductionmentioning

confidence: 91%

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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“…In rodents, genes that are implicated by QTL studies include the µ-opioid receptor 1 (OPRM1) in morphine preference 118,119 , the multiple PDZ-binding domain protein (MPDZ) in acute pentobarbital and ethanol withdrawal 120 , NPY in ethanol preference 121 , glutamic acid decarboxylase (GAD1), a GABA biosynthetic enzyme, in ethanol-induced locomotion 122 , and DRD2 and HTR1B in ethanol preference 31 . The functional allele has not been verified in any of these cases, but in other examples, effects of alleles, including artificial gene knockouts, are directly known.…”

Section: Discussionmentioning

confidence: 99%

The genetics of addictions: uncovering the genes

2005

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“…Many of these phenotypes have now been studied in "quantitative trait locus" paradigms. In these approaches, recombinant inbred (RI) mice are frequently studied [49,50]. Each strain of these RI mice contains a different complement of reassorted chromosomal segments derived from two progenitor inbred strains.…”

Section: B Studies Of Murine Strain Differences In Drug Related Phenmentioning

confidence: 99%

“Higher order” addiction molecular genetics: Convergent data from genome-wide association in humans and mice

Uhl

Drgon

Johnson

et al. 2008

Biochemical Pharmacology

127

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Family, adoption and twin data each support substantial heritability for addictions. Most of this heritable influence is not substance-specific. The overlapping genetic vulnerability for developing dependence on a variety of addictive substances suggests large roles for "higher order" pharamacogenomics in addiction molecular genetics. We and others have now completed genomewide association (GWA) studies of DNAs from individuals with dependence on a variety of addictive substances vs appropriate controls. Recently reported replicated GWA observations identify a number of genes based on comparisons between controls and European-American and African-American polysubstance abusers. Here we review the convergence between these results and data that compares control samples and a) alcohol dependent European Americans, b) methamphetamine dependent Asians and c) nicotine dependent samples from European backgrounds. We also compare these human data to quantitative trait locus (QTL) results from studies of addiction-related phenotypes in mice that focus on alcohol, methamphetamine and barbiturates. These comparisons support a genetic architecture built from largely-polygenic contributions of common allelic variants to dependence on a variety of legal and illegal substances. Many of the gene variants identified in this way are likely to alter specification and maintenance of neuronal connections. KeywordsAssociation genome scanning; substance dependence; microarray; pooled; neuronal connections * To whom correspondence should be addressed at: Molecular Neurobiology, Box 5180, Baltimore, MD 21224 phone: (410) 550-2843 x 146, fax: (410) 550-1535, guhl@intra.nida.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access A. Studies of human addiction vulnerabilitiesVulnerability to addictions is a complex trait with strong genetic influences that are largely shared by abusers of different legal and illegal addictive substances [1][2][3][4]. This conclusion comes from family, adoption and twin studies. Family studies clearly document that first degree relative (eg sibs) of addicts display greater risk for developing substance dependence than more distant relatives [1,5]. Adoption studies consistently find greater similarities between substance abuse phenotypes with biological relatives than with adoptive family members [1]. In twin studies, differences in concordance between genetically identical and fraternal twins also support heritability for vulnerability to addictions [3,[6][7][8][9][10][11][12]. Twin data allows quantitation of the amount, about 50%, of ad...

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

Cited by 36 publications

References 17 publications

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

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

The genetics of addictions: uncovering the genes

“Higher order” addiction molecular genetics: Convergent data from genome-wide association in humans and mice

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