Fine mapping and expression of candidate genes within the chromosome 10 QTL region of the high and low alcohol-drinking rats

被引:10
作者
Bice, Paula J. [1 ]
Liang, Tiebing [1 ]
Zhang, Lili [1 ]
Graves, Tamara J. [1 ]
Carr, Lucinda G. [1 ]
Lai, Dongbing [2 ]
Kimpel, Mark W. [3 ]
Foroud, Tatiana [2 ]
机构
[1] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med Hlth Informat & Translat Sci, Dept Med & Mol Genet, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA
基金
美国国家卫生研究院;
关键词
HAD and LAD rats; QTL; Fine mapping; Gene expression; QUANTITATIVE TRAIT LOCI; CREB-BINDING PROTEIN; HETEROGENEOUS STOCK; PREFERENCE; TRANSCRIPTION; MEMORY; NORMALIZATION; NEUROBIOLOGY; CONSUMPTION; INHIBITION;
D O I
10.1016/j.alcohol.2010.06.004
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
The high and low alcohol-drinking (HAD and LAD) rats were selectively bred for differences in alcohol intake. The HAD/LAD rats originated from the N/Nih heterogeneous stock developed from intercrossing eight inbred rat strains. The HAD x LAD F2 were genotyped, and a powerful analytical approach, using ancestral recombination and F2 recombination, was used to narrow a quantitative trait loci (QTL) for alcohol drinking to a 2-cM region on distal chromosome 10 that was in common in the HAD1/LAD1 and HAD2/LAD2 analyses. Quantitative real-time PCR was used to examine mRNA expression of six candidate genes (Crebbp, Trap1, Gnptg, Clcn7, Fahd1, and Mapk8ip3) located within the narrowed QTL region in the HAD1/LAD1 rats. Expression was examined in five brain regions, including the nucleus accumbens, amygdala, caudate putamen, hippocampus, and prefrontal cortex. All six genes showed differential expression in at least one brain region. Of the genes tested in this study, Crebbp and Mapk8ip3 may be the most promising candidates with regard to alcohol drinking. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:477 / 485
页数:9
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