QTL analysis of multiple behavioral measures of anxiety in mice
QTL analysis of multiple behavioral measures of anxiety in mice
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DOI：
10.1023/b:bege.0000017872.25069.44
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发表时间：
2004-05-01
影响因子：
2.6
通讯作者：
Flint, J
中科院分区：
文献类型：
--
作者：
Henderson, ND;Turri, MG;Flint, J
在由开放式竞技场、明暗箱、镜室箱、高架十字迷宫和高架方形迷宫组成的测试组合中，对1，671只小鼠进行了测试，产生了啮齿动物中超过100种假定的焦虑测量。对所有措施，加上复合措施和表型因子得分进行了数量性状基因座（QTL）分析。在17条染色体上发现了显著的LOD分数，在第1、4、7、8、14、15、18和X染色体上发现了大的且一致的QTL行为效应。染色体4和8上的QTL在很大程度上影响运动活动在家庭笼和新的环境，而染色体1，15和18上的QTL影响焦虑相关的行为。可以确定五个遗传上可分离的，交叉测试的焦虑维度：（i）在测试的低到中度焦虑区域中抑制运动活动;（ii）在高焦虑测试区域中花费的时间和活动比例减少;（iii）抑制饲养行为;（iv）增加进入新区域的潜伏期;（iv）增加进入新区域的时间和活动。（V）增加的自主反应，如通过排便和排尿评估的。QTL对交叉测试综合得分的影响模式是独特的。例如，1号染色体上的QTL强烈影响安全区域运动活动（LOD = 35）和自主反应（LOD = 16），而15号染色体上的QTL影响高焦虑区域的活动比例（LOD = 16），进入新区域的潜伏期（LOD = 36）和饲养行为（LOD = 57）。表型因子分析确定的因素，而不是交叉测试的因素上加载的单一测试。使用因子分析或测试内的主成分的数据减少遗传分析之前是不太令人满意的，比使用遗传解剖方法的原始措施和逻辑派生的复合材料。
In a test battery consisting of an open-field arena, a light-dark box, a mirror-chamber box, an elevated plus maze, and an elevated square maze, 1,671 mice were tested, generating over 100 putative measures of anxiety in rodents. Quantitative trait loci (QTL) analysis was carried out on all measures, plus composite measures and phenotypic factor scores. Significant LOD scores were found for QTL on 17 chromosomes, with large and consistent QTL behavioral effects on chromosomes 1, 4, 7, 8, 14, 15, 18, and X. QTL on chromosomes 4 and 8 largely influence locomotor activity in both home cages and novel environments, whereas QTL on chromosomes 1, 15, and 18 influence anxiety-related behaviors. Five genetically separable, cross-test dimensions of anxiety could be identified: (i) the suppression of locomotor activity in low to moderately anxiogenic regions of the tests; (ii) a shift toward proportionally less time and activity spent in high-anxiogenic test areas; (iii) the suppression of rearing behavior; (iv) increased latency to enter novel areas; ( v) increased autonomic responses, as assessed by defecation and urination. Patterns of QTL influence on cross-test composite scores were distinctive. For example, the QTL on chromosome 1 strongly influenced safe-area locomotor activity ( LOD = 35) and autonomic responses ( LOD = 16), whereas the QTL on chromosome 15 influenced the proportion of activity in high-anxiogenic areas ( LOD = 16), latency to enter novel areas ( LOD = 36) and rearing behavior ( LOD = 57). Phenotypic factor analysis identified factors heavily loaded on single tests, rather than cross-test factors. The use of factor analysis or within-test principal components for data reduction before genetic analysis was less satisfactory than using genetic dissection methods on the original measures and logically derived composites.