Terenina-Rigaldie Elena, Moisan Marie-Pierre, Colas Anthony, Beaugé Françoise, Shah Kavita V, Jones Byron C, Mormède Pierre
Laboratoire de Neurogénétique et Stress, UMR 1243 INRA--Université Victor Segalen, Inserm U471, Institut François Magendie, Bordeaux, France.
Pharmacogenetics. 2003 Sep;13(9):543-54. doi: 10.1097/01.fpc.0000054120.14659.8c.
The aim of this study was to analyse the genetic basis of excessive ethanol consumption and its relationship with emotional reactivity. The high-ethanol preferring line of rats used is characterized by a: (i) high voluntary consumption of alcohol; (ii) high sensitivity to taste reinforcement (saccharine, quinine); (iii) high locomotor activity in a novel environment; and (iv) low emotional reactivity, these features being opposite in the Wistar-Kyoto (WKY) rat strain. The F2 population demonstrated a very large variability in these behavioural traits, and factor analysis revealed that these characteristics appear to be largely unrelated to each other. The molecular bases for these differences were investigated by quantitative trait loci (QTL) analysis. For this purpose, the 196 F2 rats were genotyped with regularly distributed markers on the whole genome, and genetic linkage maps were generated for all subsequent QTL analyses. A locus with a maximum LOD score of 7.6 and accounting for approximately 61% of the genetic variance of the trait in the F2 population was detected on chromosome 4 for alcohol drinking. In the same region, we found a QTL related to the reinforcement properties of saccharin, with a significant LOD score of 4.9 and explaining 46% of the variance of the trait. Other significant QTL were found for plus maze behaviour and open field activity on chromosome 1. Current research aims to identify the gene(s) involved.
本研究的目的是分析过量乙醇摄入的遗传基础及其与情绪反应性的关系。所使用的高乙醇偏好大鼠品系具有以下特点:(i)酒精自愿摄入量高;(ii)对味觉强化(糖精、奎宁)敏感;(iii)在新环境中运动活性高;(iv)情绪反应性低,而这些特征在Wistar-Kyoto(WKY)大鼠品系中则相反。F2群体在这些行为特征上表现出很大的变异性,因子分析表明这些特征似乎在很大程度上彼此无关。通过数量性状位点(QTL)分析研究了这些差异的分子基础。为此,对196只F2大鼠进行了全基因组均匀分布标记的基因分型,并为所有后续的QTL分析构建了遗传连锁图谱。在4号染色体上检测到一个最大LOD得分为7.6且占F2群体该性状遗传方差约61%的位点与酒精饮用有关。在同一区域,我们发现了一个与糖精强化特性相关的QTL,其显著LOD得分为4.9,解释了该性状46%的方差。在1号染色体上还发现了与十字迷宫行为和旷场活动相关的其他显著QTL。目前的研究旨在鉴定其中涉及的基因。