Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred High and Low Alcohol Sensitive selectively bred rat lines

Radcliffe, Richard A.; Bludeau, Pequita; Asperi, William; Fay, Tina; Deng, Xin‐Sheng; Erwin, V. Gene; Deitrich, Richard A.

doi:10.1007/s00213-006-0512-2

Cited by 14 publications

(27 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Genes in the highest nodes are connected to the largest number of gene sets and are thus considered more highly supported candidates by empirical evidence. The six QTLs that overlap with the Chr 3 hypothermia QTL are Alcp3 (Peirce et al 1998), Ap6q (Tarantino et al 1998), Letohc1 (Belknap and Atkins 2001), Lore10 (Bennett et al 2006) from mouse and Alcrsp17 (Radcliffe et al 2006) and Alcrsp28 (Radcliffe et al 2009) from rat. The gene expression sets that intersect with positional candidates from the QTL interval are ‘GS128167: Lewis vs. Fischer GABA’ (Sharp et al 2011) with differential expression in the nucleus accumbens (NA) shell GABA neurons projecting to ventral pallidum in these two strains, ‘GS31783: Gx Corr Neo Cortex’ (Phillips et al 1994) where the gene expression in BXD Neocortex ILM6v1.1 (Feb08) RankInv microarray data from GeneNetwork.org was correlated with preference for 10% ethanol (g/kg) in a two-bottle choice, ‘GS3647: Et Pref Meta Analysis’ (Mulligan et al 2006) consisting of genes from the meta-analysis of differential expression in six isogenic and three selected lines with elevated voluntary ethanol consumption, ‘GS87303: Alcohol preferring vs. non-preferring Rats’ (Edenberg et al 2005) consisting of differential expression in the hippocampus of inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats, and ‘GS128167: DiffExprs EtOH NA’ (Rodd et al 2008) consisting of differential expression in the NA of inbred alcohol-preferring mice…”

Section: Resultsmentioning

confidence: 99%

Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J × 129S1/SvImJ inbred mouse cross

et al. 2012

View full text Add to dashboard Cite

Individual variation in sensitivity to acute ethanol (EtOH) challenge is associated with alcohol drinking and is a predictor of alcohol abuse. Previous studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse strains differ in responses on certain measures of acute EtOH intoxication. To gain insight into genetic factors contributing to these differences, we performed quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration in a B6 × S1 F2 population. We confirmed that S1 showed greater EtOH-induced hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL analysis revealed several additive and interacting loci for various phenotypes, as well as examples of genotype interactions with sex. QTLs for different EtOH phenotypes were largely non-overlapping, suggesting separable genetic influences on these behaviors. The most compelling main-effect QTLs were for hypothermia on chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with loci repeatedly linked to EtOH drinking in previous mouse studies. The architecture of the traits we examined was complex but clearly amenable to dissection in future studies. Using integrative genomics strategies, plausible functional and positional candidates may be found. Uncovering candidate genes associated with variation in these phenotypes in this population could ultimately shed light on genetic factors underlying sensitivity to EtOH intoxication and risk for alcoholism in humans. Electronic supplementary material The online version of this article (doi:10.1007/s00335-012-9394-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J × 129S1/SvImJ inbred mouse cross

et al. 2012

View full text Add to dashboard Cite

show abstract

“…1975; O’Connor et al . 1999; Ponomarev & Crabbe 2004; Radcliffe et al . 2006; Radlow & Hurst 1985; Ramchandani et al .…”

Section: Discussionunclassified

A major QTL for acute ethanol sensitivity in the alcohol tolerant and non‐tolerant selected rat lines

Radcliffe

Erwin

Bludeau

et al. 2009

Genes Brain and Behavior

View full text Add to dashboard Cite

The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F 2 intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F 2 offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR) and blood ethanol at regain of the righting reflex (BECRR). F 2 rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2 and 3. Highly significant QTLs for LORR duration (LOD = 12.4) and BECRR (LOD = 5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.

show abstract

“…The “Addict” F1 and F2 offspring displayed increased cocaine self‐administration, while no effect on cocaine self‐administration was detected in the “Non‐addict” F1 and F2 offspring (Le et al ., ). Previous studies that have separated mouse drug‐response into high and low responders have identified numerous genetic differences between these sub‐populations (Radcliffe et al ., ; He et al ., ; Belknap et al ., ). These findings provided support for a gene by environment interaction that can greatly alter the effects of paternal cocaine exposure.…”

Section: Cocainementioning

confidence: 99%

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Goldberg

Gould

2018

Eur J of Neuroscience

View full text Add to dashboard Cite

Addictions are highly heritable disorders, with heritability estimates ranging from 39% to 72%. Multiple studies suggest a link between paternal drug abuse and addiction in their children. However, patterns of inheritance cannot be explained purely by Mendelian genetic mechanisms. Exposure to drugs of abuse results in epigenetic changes that may be passed on through the germline. This mechanism of epigenetic transgenerational inheritance may provide a link between paternal drug exposure and addiction susceptibility in the offspring. Recent studies have begun to investigate the effect of paternal drug exposure on behavioral and neurobiological phenotypes in offspring of drug-exposed fathers in rodent models. This review aims to discuss behavioral and neural effects of paternal exposure to alcohol, cocaine, opioids, and nicotine. Although a special focus will be on addiction-relevant behaviors, additional behavioral effects including cognition, anxiety, and depressive-like behaviors will be discussed.

show abstract

Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred High and Low Alcohol Sensitive selectively bred rat lines

Abstract: QTL mapping in crosses derived from the IHAS1 and ILAS1 has successfully identified loci related to alcohol sensitivity. Recombinant congenics are now being bred to more finely map the confirmed QTLs.

Cited by 14 publications

References 65 publications

Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J × 129S1/SvImJ inbred mouse cross

Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J × 129S1/SvImJ inbred mouse cross

A major QTL for acute ethanol sensitivity in the alcohol tolerant and non‐tolerant selected rat lines

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Contact Info

Product

Resources

About