Li X C, Karadsheh M S, Jenkins P M, Brooks J C, Drapeau J A, Shah M S, Lautner M A, Stitzel J A
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
Genes Brain Behav. 2007 Jul;6(5):401-10. doi: 10.1111/j.1601-183X.2006.00266.x. Epub 2006 Sep 8.
Several studies have demonstrated that there are genetic influences on free-choice oral nicotine consumption in mice. In order to establish the genetic architecture that underlies individual differences in free-choice nicotine consumption, quantitative trait loci (QTL) mapping was used to identify chromosomal regions that influence free-choice nicotine consumption in male and female F(2) mice derived from a cross between C57BL/6J and C3H/HeJ mice. These two mouse strains were chosen not only because they differ significantly for oral nicotine consumption, but also because they are at or near phenotypic extremes for all measures of nicotine sensitivity that have been reported. A four-bottle choice paradigm was used to assess nicotine consumption over an 8-day period. The four bottles contained water or water supplemented with 25, 50 or 100 microg/ml of nicotine base. Using micrograms of nicotine consumed per milliliter of total fluid consumed per day as the nicotine consumption phenotype, four significant QTL were identified. The QTL with the largest LOD score was located on distal chromosome 1 (peak LOD score = 15.7). Other chromosomes with significant QTL include central chromosome 4 (peak LOD score = 4.1), proximal chromosome 7 (peak LOD score = 6.1) and distal chromosome 15 (peak LOD score = 4.8). These four QTL appear to be responsible for up to 62% of the phenotypic variance in oral nicotine consumption.
多项研究表明，基因对小鼠自由选择口服尼古丁的行为存在影响。为了确定自由选择尼古丁消费个体差异背后的遗传结构，采用数量性状基因座（QTL）定位法来识别影响C57BL/6J和C3H/HeJ小鼠杂交产生的雄性和雌性F(2)小鼠自由选择尼古丁消费的染色体区域。选择这两种小鼠品系不仅是因为它们在口服尼古丁消费方面存在显著差异，还因为它们在已报道的所有尼古丁敏感性测量指标上处于或接近表型极端。采用四瓶选择范式在8天时间内评估尼古丁消费量。四个瓶子分别装有水或添加了25、50或100微克/毫升尼古丁碱的水。以每天每毫升总液体消耗中消耗的尼古丁微克数作为尼古丁消费表型，确定了四个显著的QTL。LOD得分最高的QTL位于1号染色体远端（峰值LOD得分 = 15.7）。其他含有显著QTL的染色体包括4号染色体中部（峰值LOD得分 = 4.1）、7号染色体近端（峰值LOD得分 = 6.1）和15号染色体远端（峰值LOD得分 = 4.8）。这四个QTL似乎对口服尼古丁消费中高达62%的表型变异负责。
