Boyle Alan E, Gill Kathryn J
Psychiatry Department, McGill University, Montreal, QC, Canada, H3G 1B3.
Mamm Genome. 2009 Jan;20(1):34-42. doi: 10.1007/s00335-008-9159-0. Epub 2008 Dec 13.
Previous research utilizing the AcB/BcA recombinant congenic strains (RCS) of mice mapped provisional quantitative trait loci (QTLs) for the psychostimulant effects of nicotine to multiple regions on chromosomes 7, 11, 12, 14, 16, and 17. The current study was designed to confirm these QTLs in an A/J (A) x C57Bl/6J (B6) F2 cross and a panel of B6.A chromosome substitution strains (CSS). The panel of B6.A CSS consists of 21 strains, each carrying a different A/J chromosome on a B6 background. The A x B6 F2, CSS, A, and B6 mice were tested for sensitivity to the effects of nicotine on locomotor activity using a computerized open-field apparatus. In A x B6 F2 mice two QTLs were identified which confirm those previously observed in the AcB/BcA RCS. Significant differences in the expression of nicotine-induced activity were associated with loci on chromosome 11 (D11Mit62) and chromosome 16 (D16Mit131) in the A x B6 F2. At the chromosome 11 QTL, an A allele was associated with lower nicotine-induced activity scores relative to the B6. In contrast, the A allele was associated with greater relative nicotine activity values for the chromosome 16 QTL. A survey of the CSS panel confirmed the presence of QTLs for nicotine activation on chromosomes 2, 14, 16, and 17 previously identified in the AcB/BcA RCS. In the informative CSS strains, A alleles were consistently associated with greater nicotine-induced activity scores compared to the B6. The results of the present study are the first to validate QTLs for sensitivity to the effects of nicotine across multiple strains of mice. QTLs on chromosomes 2, 11, 14, 16, and 17 were confirmed in CSS and/or F2 mice. Significantly, the identification of a QTL on chromosome 16 has now been replicated in three crosses derived from the A and B6 progenitors.
以往利用小鼠的AcB/BcA重组近交系（RCS）开展的研究，将尼古丁精神兴奋作用的临时数量性状基因座（QTL）定位到了7号、11号、12号、14号、16号和17号染色体的多个区域。当前研究旨在通过A/J（A）×C57Bl/6J（B6）F2杂交以及一组B6.A染色体代换系（CSS）来确认这些QTL。B6.A CSS组由21个品系组成，每个品系在B6背景上携带一条不同的A/J染色体。使用计算机化旷场装置对A×B6 F2、CSS、A和B6小鼠进行尼古丁对运动活动影响的敏感性测试。在A×B6 F2小鼠中鉴定出两个QTL，证实了先前在AcB/BcA RCS中观察到的那些QTL。在A×B6 F2中，尼古丁诱导活动表达的显著差异与11号染色体（D11Mit62）和16号染色体（D16Mit131）上的基因座相关。在11号染色体QTL处，相对于B6，A等位基因与较低的尼古丁诱导活动得分相关。相比之下，对于16号染色体QTL，A等位基因与较高的相对尼古丁活动值相关。对CSS组的调查证实了先前在AcB/BcA RCS中鉴定出的2号、14号、16号和17号染色体上尼古丁激活QTL的存在。在信息丰富的CSS品系中，与B6相比，A等位基因始终与更高的尼古丁诱导活动得分相关。本研究结果首次在多个小鼠品系中验证了对尼古丁作用敏感性的QTL。在CSS和/或F2小鼠中确认了2号、11号、14号、16号和17号染色体上的QTL。重要的是，现已在源自A和B6祖系的三个杂交组合中重复鉴定出16号染色体上的一个QTL。
