Sex- and lineage-specific inheritance of depression-like behavior in the rat
Sex- and lineage-specific inheritance of depression-like behavior in the rat
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DOI：
10.1007/s00335-004-2326-z
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发表时间：
2004-08-01
期刊：
影响因子：
2.5
通讯作者：
Redei, EE
中科院分区：
文献类型：
--
作者：
Solberg, LC;Baum, AE;Redei, EE
Wistar-京都(WKY)大鼠表现出与人类抑郁症内表型相似的生理和行为特征。在强迫游泳试验(FST)中，WKY表现出行为绝望的特征，增加了不动，减少了爬升。为了定位与FST行为连锁的遗传座位，我们对WKY×Fisher 344(F344)正反交分离F2代进行了数量性状基因座(QTL)分析。利用基于线性模型的基因组扫描来考虑协变量(性别或血统)与QTL的互作效应，确定了四个影响攀登行为的显著QTL。此外，我们分别确定了3个、7个和2个暗示攀登、静止和游泳的QTL。其中一个基因座是多效性的，既影响静止也影响攀爬。在人类连锁研究中发现，这些QTL中有几个表现出性别和/或血统依赖的效应。一种同时搜索策略确定了三个上位性攀登轨迹对。使用多元回归分析来描述这些QTL的联合作用，并阐明性别和血统依赖的效应。对于复杂性状，FST行为受多个效应较小的QTL的影响，每个QTL的贡献率为5%-10%，对表型方差的贡献率为10%-30%。在这项研究中定位的一些基因座共享与先前在小鼠中发现的情绪性QTL以及通过连锁或基因组扫描分析识别的人类严重抑郁症或双相情感障碍的易感基因座重叠的候选区域。这些基因座在不同物种中的存在表明，这些QTL可能代表了导致情绪障碍的普遍遗传因素。
The Wistar-Kyoto (WKY) rat exhibits physiological and behavioral similarities to endophenotypes of human depression. In the forced swim test (FST), a well-characterized antidepressant-reversible test for behavioral despair in rodents, WKYs express characteristics of behavioral despair; increased immobility, and decreased climbing. To map genetic loci linked to behavior in the FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2 generation of a WKY x Fisher 344 (F344) reciprocal intercross. Using linear-model-based genome scans to include covariate (sex or lineage)by-QTL interaction effects, four significant QTL influencing climbing behavior were identified. in addition, we identified three, seven, and two suggestive QTL for climbing, immobility, and swimming, respectively. One of these loci was pleiotropic, affecting both immobility and climbing. As found in human linkage studies, several of these QTL showed sex- and/or lineage-dependent effects. A simultaneous search strategy identified three epistatic locus pairs for climbing. Multiple regression analysis was employed to characterize the joint contributions of these QTL and to clarify the sex- and lineage-dependent effects. As expected for complex traits, FST behavior is influenced by multiple QTL of small effect, each contributing 5%-10%, accounting for a total 10%-30% of the phenotypic variance. A number of loci mapped in this study share overlapping candidate regions with previously identified emotionality QTL in mice as well as with susceptibility loci recognized by linkage or genome scan analyses for major depression or bipolar disorder in humans. The presence of these loci across species suggests that these QTL may represent universal genetic factors contributing to mood disorders.