QTL ANALYSIS OF FEAR-RELATED BEHAVIOR IN RODENTS

基因对焦虑相关疾病的影响是毋庸置疑的，但 人们对这种贡献的性质仍然知之甚少。我们提出 进行恐惧的数量性状基因座（QTL）研究- 作为理解的第一步， 可能的遗传机制。 一个广泛的测试电池将 用于表征小鼠中与恐惧相关的行为， 识别与一般活动、恐惧症的潜在混淆， 趋触性 我们将使用简单的单变量QTL作图 技术和最近的多变量映射技术来定位 F2小鼠中的QTL。 这些方法在以下方面非常成功： 在植物和最近的动物研究中定位QTL。 的 这项提议中概述的研究将使用一种近交系小鼠， 是从那些被选择性地培育出来的品系中衍生出来的， 相关行为。 小鼠染色剂（由DeFries开发）是 选择性繁殖的差异，在开放领域的活动;两个高（H1和 H2）和两个低水平菌株（L1和L2）。H-L菌株 也不同的露天排便（L多H）。 F2混合动力车将成为 由L_1-H_1杂交和L_2-H_2杂交发展而来。 F2小鼠将 在笼中进行活动评估和几项恐惧措施- 相关和抑郁行为。 大约800只F2动物将 在每个交叉中评分（总共1600只动物），并且来自这些相同的 将使用84个微卫星筛选动物的多态性。 使用两种方法测试QLT方法的可重复性的策略 从小鼠衍生的杂交应该作为一个严格的测试， QTL方法，也可以促进识别恐惧- 人类的相关基因

A genetic contribution to anxiety-related disorders is not in doubt, but the nature of that contribution is still poorly understood. We propose to conduct a quantitative trait loci (QTL) study of fear- related/emotional behavior in the mouse as a first step to understanding possible genetic mechanisms in humans. An extensive test battery will be used to characterize fear-related behaviors in the mice and to identify potential confounds with general activity, photophobia, and thigmotaxis. We will use both simple univariate QTL mapping techniques and more recent multivariate mapping techniques to locate QTLs in F2 mice. These methods have been remarkably successful in mapping QTLs in plants and more recently in animal studies. The studies outlined in this proposal will use an inbred strain of mice that was derived from lines that were selectively bred for what may be fear- related behaviors. The mouse stains (developed by DeFries) were selectively bred for differences in open-field activity; two high (H1 and H2) and two low (L1 and L2) strains were developed. The H-L strains also differ in open-field defecation (L more H). F2 hybrids will be developed from L1 - H1 crosses and L2-H2 crosses. The F2 mice will be evaluated for activity in home cage and several measures of fear- related and depressive behaviors. Approximately 800 F2 animals will be scored in each cross (1600 animals total) and DNA from these same animals will be screened for polymorphisms using 84 microsatellites. The strategy of testing the replicability of the QLT method using two crosses derived from the mouse should serve as a rigorous test of the QTL methodology and could also facilitate the identification of fear- related genes in humans.