Genetics of ethanol-induced locomotor activation:: detection of QTLs in a C57BL/6JxDBA/2JF2 intercross
Genetics of ethanol-induced locomotor activation:: detection of QTLs in a C57BL/6JxDBA/2JF2 intercross
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DOI：
10.1007/s003359900906
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发表时间：
1998-12-01
期刊：
影响因子：
2.5
通讯作者：
McCaughran, J
中科院分区：
文献类型：
--
作者：
Hitzemann, R;Cipp, L;McCaughran, J
中等剂量的乙醇（1 - 2 g/kg）显著增加某些近交系小鼠品系（例如DBA/2J（D2））的自发活动，但对其他品系（例如C57 BL/6J（B6））的影响相对较小。在本研究中，我们进行了全基因组搜索B6D2 F-2互交（N = 925）的数量性状位点（QTL）与运动反应。在2号染色体上检测到一个LOD值为8.4的QTL，该QTL占表型方差的11.4%，占遗传方差的30%左右。Chr 2上的QTL与先前描述的乙醇偏好/消费的QTL在相同的一般区域（Rodriguez等，Alcohol Clin Exp Res 19，367，1995;梅洛等，Nat Genet 13，147，1996;菲利普斯等人，《哺乳动物基因组》，出版中），急性乙醇戒断（Buck等，J.Neurosci 17，3946，1997）和一氧化二氮戒断严重性（Belknap等，Behav Genet 23，213，1993）。感兴趣的区域中的合乎逻辑的候选基因是合成GABA的酶，谷氨酸脱羧酶1（GadI）。
Moderate doses of ethanol (1-2 g/kg) markedly increase locomotor activity in some inbred mouse strains, for example, the DBA/2J (D2), but have relatively little effect in other strains, for example, the C57BL/6J (B6). In the present study, we conducted a genome-wide search in a B6D2 F-2 intercross (N = 925) for quantitative trait loci (QTLs) associated with the locomotor response. A QTL with a LOD score of 8.4 was detected on Chromosome (Chr) 2; this QTL accounted for 11.4% of the phenotypic variance and approximately 30% of the genetic variance. The QTL on Chr 2 is in the same general region as QTLs previously described for ethanol preference/consumption (Rodriguez et al. Alcohol Clin Exp Res 19, 367, 1995; Melo et al. Nat Genet 13, 147, 1996; Phillips et al. Mamm Genome, in press), acute ethanol withdrawal (Buck et al. J. Neurosci 17, 3946, 1997) and nitrous oxide withdrawal severity (Belknap et al. Behav Genet 23, 213, 1993). A logical candidate gene in the region of interest is the enzyme which synthesizes GABA, glutamic acid decarboxylase 1 (GadI).