Hitzemann R, Cipp L, Demarest K, Mahjubi E, McCaughran J
Departments of Psychiatry and Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794-8101, USA.
Mamm Genome. 1998 Dec;9(12):956-62. doi: 10.1007/s003359900906.
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 F2 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).
中等剂量的乙醇（1 - 2克/千克）能显著增加某些近交系小鼠品系的运动活性，例如DBA/2J（D2）品系，但对其他品系，如C57BL/6J（B6）品系的影响相对较小。在本研究中，我们在B6D2 F2杂交群体（N = 925）中进行了全基因组搜索，以寻找与运动反应相关的数量性状基因座（QTL）。在第2号染色体（Chr）上检测到一个LOD得分为8.4的QTL；该QTL占表型变异的11.4%，约占遗传变异的30%。第2号染色体上的QTL与先前描述的乙醇偏好/消耗量（Rodriguez等人，《酒精临床与实验研究》19，367，1995；Melo等人，《自然遗传学》13，147，1996；Phillips等人，《哺乳动物基因组》，即将发表）、急性乙醇戒断（Buck等人，《神经科学杂志》17，3946，1997）和氧化亚氮戒断严重程度（Belknap等人，《行为遗传学》23，213，1993）的QTL位于相同的大致区域。该感兴趣区域的一个合理候选基因是合成γ-氨基丁酸（GABA）的酶，即谷氨酸脱羧酶1（GadI）。
