Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines.
Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines.
复制标题
对来自高和低酒精敏感选择性繁殖的大鼠品系的 F2 群体进行急性乙醇耐受和过敏的短期选择。
DOI：
10.1016/j.alcohol.2007.10.001
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Deitrich,RichardA
中科院分区：
文献类型：
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作者：
Radcliffe,RichardA;Bludeau,Pequita;Deng,Xin-Sheng;Erwin,VGene;Deitrich,RichardA
以往的研究已经确定了数量性状基因座（QTL）的近交高，低酒精敏感大鼠（IHAS 1和ILAS 1）的品系。菌株的最初开发涉及基于标准剂量乙醇后翻正反射（LORR）丧失的持续时间选择乙醇敏感性。本文证实了一些这些QTL使用短期选择程序的基础上在LORR和恢复的翻正反应的血液乙醇水平之间的差异。通过IHAS 1和ILAS 1大鼠的相互杂交，开发了大鼠的F2群体。使用δ血液乙醇浓度（dBEC）作为选择性状进行五代选择，其中dBEC=BECLR（翻正反射丧失时的BEC）-BECRR（翻正反射恢复时的BEC）。这些品系被标记为耐受（TOL）或敏感（SENS）。使用先前已发现与染色体1、2、5、12和13上的QTL连锁的DNA标记，对每个品系中每代约三分之一的后代进行基因分型。到第五代选择时，品系在dBEC、BECRR和LORR持续时间方面表现出非常大的差异; BECLR在选择过程中表现出很小的分离，并且失去翻正反射的潜伏期没有表现出任何差异。在SENS系中，1、5、12和13号染色体上标记的IHAS等位基因频率增加，而在TOL系中ILAS等位基因频率增加。这些结果与之前的两个QTL研究结果一致。在2号染色体上，选择导致两个品系中ILAS等位基因的积累。这项研究提供了独立的确认的位置上的染色体1，5，12和13的乙醇敏感性的QTL。这也表明LORR持续时间的遗传差异主要由dBEC表型介导。
Previous studies have identified quantitative trait loci (QTL) in the inbred high and low alcohol-sensitive rat (IHAS1 and ILAS1) strains. The original development of the strains involved selection for ethanol sensitivity based on duration of the loss of the righting reflex (LORR) after a standard dose of ethanol. This paper confirms some of these QTL using a short-term selection procedure based on the difference between the blood ethanol level at LORR and regain of the righting response. An F2population of rats was developed by a reciprocal cross of IHAS1 and ILAS1 rats. Selection for five generations was carried out using delta-blood ethanol concentration (dBEC) as the selection trait, where dBEC=BECLR (BEC at loss of righting reflex)−BECRR (BEC at regain of righting reflex). The lines were labeled tolerant (TOL) or sensitive (SENS). Approximately one-third of the offspring for each generation in each line were genotyped using DNA markers that had been previously found to be linked to QTL on chromosomes 1, 2, 5, 12, and 13. By the fifth generation of selection, the lines showed a very large difference in dBEC, BECRR, and duration of LORR; BECLR showed little segregation during the selection, and latency to lose the righting reflex showed none. IHAS allele frequency increased in the SENS line for markers on chromosomes 1, 5, 12, and 13 while ILAS allele frequency increased in the TOL line. These results were in good agreement with the two previous QTL studies. On chromosome 2, the selection resulted in an accumulation of ILAS alleles in both lines. This study provides independent confirmation of the location of QTL on chromosomes 1, 5, 12, and 13 for ethanol sensitivity. It also suggests that genetic differences in duration of LORR are mediated primarily by the dBEC phenotype.