Genetic relationship between anxiety-related and fear-related behaviors in BXD recombinant inbred mice
Genetic relationship between anxiety-related and fear-related behaviors in BXD recombinant inbred mice
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DOI：
10.1097/fbp.0b013e32830c368c
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发表时间：
2009-03-01
影响因子：
1.6
通讯作者：
Holmes, Andrew
中科院分区：
文献类型：
--
作者：
Brigman, Jonathan L.;Mathur, Poonam;Holmes, Andrew
情绪和焦虑障碍以及模拟这些障碍的啮齿动物表型测量具有很强的遗传成分。使用各种测定来研究恐惧相关和焦虑相关行为、表型遗传修饰小鼠的神经生物学基础，并阐明这些行为的药理学调节以用于药物开发。然而，早期的工作表明，不同的性状措施介导的部分重叠，但最终不同的遗传因素。在这项研究中，我们评估了一个新的面板的23 C57 BL/6 J x DBA/2 J（BXD）重组近交系的巴甫洛夫恐惧条件反射和焦虑样行为（新的开放领域，高架十字迷宫），以及感觉（声惊吓，惊吓的前脉冲抑制）和运动（基线协调和学习加速旋转杆）功能的各种性状指标。结果表明，性状在不同品系间呈连续分布，具有中等到较强的R-2值。主成分分析将数据分解为五个因素：因子1加载恐惧相关的特征，因子2加载高架十字迷宫措施以及上下文恐惧，因子3加载新的开放领域措施和十字迷宫封闭臂条目，因子4加载旋转棒运动功能，因子5加载声惊吓和前脉冲抑制。这些数据增加了证据表明，小鼠措施的恐惧和焦虑样性状反映了不同的结构介导的可分离的基因变异。Behavioural Pharmacology 20：204-209（C）2009年威科健康|利平科特威廉姆斯&威尔金斯。
Mood and anxiety disorders, and rodent phenotypic measures modeling these disorders, have a strong genetic component. Various assays are used to study the neurobiological basis of fear-related and anxiety-related behaviors, phenotype genetically modified mice, and elucidate pharmacological modulation of these behaviors for medication development. Earlier work, however, suggests that different trait measures are mediated by partly overlapping but ultimately distinct genetic factors. In this study, we assessed a novel panel of 23 C57BL/6J x DBA/2J (BXD) recombinant inbred strains on various trait measures of Pavlovian fear conditioning and anxiety-like behavior (novel open field, elevated plus-maze), as well as sensory (acoustic startle, prepulse inhibition of startle) and motor (baseline coordination and learning on accelerating rotarod) function. Results showed that traits were continuously distributed across strains and had modest to strong R-2 values. Principal components analysis resolved the data into five factors: factor 1 loaded fear-related traits, factor 2 loaded elevated plus-maze measures as well as context fear, factor 3 loaded novel open field measures and plus-maze closed arm entries, factor 4 loaded rotarod motor function, and factor 5 loaded acoustic startle and prepulse inhibition. These data add to evidence that murine measures of fear-like and anxiety-like traits reflect distinct constructs mediated by dissociable gene variants. Behavioural Pharmacology 20:204-209 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.