Quantitative trait loci (QTL) applications to substances of abuse: Physical dependence studies with nitrous oxide and ethanol in BXD mice

Belknap, John K.; Metten, Pamela; Helms, Melinda L.; O’Toole, L. A.; Angeli-Gade, S.; Crabbe, John C.; Phillips, Tamara J.

doi:10.1007/bf01067426

Cited by 94 publications

(73 citation statements)

References 42 publications

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“…Although several groups have used various RI series for the provisional mapping of QTLs influencing several ethanol related responses (McClearn et al 1992;Belknap et al 1993;Crabbe et al 1994b;Rodriguez et al 1995;Markel et al 1996a), our F2 results strongly encourage confirmation or disproof of provisional QTLs from RI-mapping experiments using large F2 stocks.…”

Section: Discussionmentioning

confidence: 53%

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

Markel¹,

Bennett²,

Beeson³

et al. 1997

Genome Res.

101

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Initial insensitivity to alcohol is a strong predictor of human alcoholism, a widespread and heritable health problem. The Long Sleep and Short Sleep lines of mice were developed by genetic selection for high or low alcohol sensitivity. We have identified seven quantitative trait loci (QTLs) specifying differences in alcohol sensitivity using intercross progeny from these selected strains. These QTLs (LoreI-LoreT) together account for -60% of the total genetic variance for this trait. This represents the first report of linkages for genes influencing alcohol action in any mammalian system using stringent, genome-wide mapping criteria.

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Section: Discussionmentioning

confidence: 53%

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

Markel¹,

Bennett²,

Beeson³

et al. 1997

Genome Res.

101

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“…QTLs obtained in one set of RIs can be further confirmed in other sets of RIs, in F2 or backcross progeny of the parental strains (from which RIs are derived), or in their congenic strains (see examples in Belknap et al 1992a;Crabbe et al 1994).…”

Section: Introductionmentioning

confidence: 86%

Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice

Tafti

Chollet

Valatx

et al. 1999

Journal of Sleep Research

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SUMMARYSleep is a complex trait controlled by many genes, the environment, and probably by gene±environment interactions. Among different approaches to the genetics of sleep, analysis of quantitative traits (QTL) has the advantage of being able to detect, along with major genes, minor and/or modifier genes influencing different quantitative aspects of sleep. We have used QTL analysis in two different sets of recombinant inbred (RI) strains and sought for confirmation of several localizations in eight histocompatibility congenic strains. Several QTLs were identified which influenced the amount of vigilance states. In a first RI series (seven strains) the only QTLs identified were those affecting paradoxical sleep (PS), whereas analysis in a second RI series (25 strains) revealed QTLs influencing PS, slow-wave sleep, and total sleep. Among these, a single QTL on chromosome 5 was associated with all vigilance states, suggesting the presence of a major gene influencing a basic aspect of sleep amount. Search for candidate genes around the identified QTLs indicated several immune related genes that have been implicated in sleep regulation. Transgenic animals carrying loss-of-function and/or gainof-function mutations affecting these candidate genes should confirm these findings.

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“…We first mapped expression changes identified in our studies versus chromosomal regions assigned to confirmed QTLs for acute locomotor responses to ethanol, acute ethanol withdrawal, or ethanol preference drinking (for review, see Belknap et al, 1993). Other ethanol behavioral QTLs might also involve genes identified in these studies, but we focused on these behaviors for reasons noted above.…”

Section: Correlation Of Expression Profiling With Qtl Studies On Ethamentioning

confidence: 99%

Ethanol-Responsive Brain Region Expression Networks: Implications for Behavioral Responses to Acute Ethanol in DBA/2J versus C57BL/6J Mice

Kerns¹,

Ravindranathan²,

Hassan³

et al. 2005

J. Neurosci.

214

274

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Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three brain regions of the mesolimbic reward pathway of these strains. Expression profiling included examination of both differences in gene expression 4 h after saline injection or acute ethanol (2 g/kg). Using a rigorous stepwise method for microarray analysis, we identified 788 genes differentially expressed in control DBA/2J versus C57BL/6J mice and 307 ethanolregulated genes in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. There were strikingly divergent patterns of ethanol-responsive gene expression in the two strains. Ethanol-responsive genes also showed clustering at discrete chromosomal regions, suggesting local chromatin effects in regulation. Ethanol-regulated genes were generally related to neuroplasticity, but regulation of discrete functional groups and pathways was brain region specific: glucocorticoid signaling, neurogenesis, and myelination in the prefrontal cortex; neuropeptide signaling and developmental genes, including factor Bdnf, in the nucleus accumbens; and retinoic acid signaling in the ventral tegmental area. Bioinformatics analysis identified several potential candidate genes for quantitative trait loci linked to ethanol behaviors, further supporting a role for expression profiling in identifying genes for complex traits. Brain regionspecific changes in signaling and neuronal plasticity may be critical components in development of lasting ethanol behavioral phenotypes such as dependence, sensitization, and craving.

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Quantitative trait loci (QTL) applications to substances of abuse: Physical dependence studies with nitrous oxide and ethanol in BXD mice

Cited by 94 publications

References 42 publications

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice

Ethanol-Responsive Brain Region Expression Networks: Implications for Behavioral Responses to Acute Ethanol in DBA/2J versus C57BL/6J Mice

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