Neurobehavioral mutants identified in an ENU-mutagenesis project
Neurobehavioral mutants identified in an ENU-mutagenesis project
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DOI：
10.1007/s00335-007-9035-3
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发表时间：
2007-08-01
期刊：
影响因子：
2.5
通讯作者：
Goldowitz, Dan
中科院分区：
文献类型：
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作者：
Cook, Melloni N.;Dunning, Jonathan P.;Goldowitz, Dan
我们报告了一组行为筛选试验，成功地确定了几个神经行为突变体之间的大规模ENU诱变小鼠种群。根据一系列行为任务中的异常表现，对大量ENU诱变小鼠进行中枢神经系统功能异常筛查。我们开发并使用了行为任务的高通量筛选来检测行为离群值。已经鉴定了12个突变体谱系，代表了广泛的行为表型。具体来说，我们已经确定了两个开放领域突变体（一个表现出过度运动，其他hypolocomotion），四个尾部悬挂突变体（所有显示增加不动性），一个伤害感受突变体（显示对热痛的异常反应），两个前脉冲抑制突变体（表现出对惊吓反应的不良抑制），一种焦虑相关的突变体（在明/暗测试中显示出减少的焦虑），和一个学习和记忆突变体（显示出对条件刺激的减少的反应）。这些发现突出了一组用于高通量筛选以识别神经行为突变体的行为任务的实用性。进一步分析（即，行为和遗传作图研究）正在进行中，其最终目标是鉴定与人类疾病相关的新基因和小鼠模型以及鉴定新的治疗靶点。
We report on a battery of behavioral screening tests that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU-mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and used a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open-field mutants (one displaying hyperlocomotion, the other hypolocomotion), four tail-suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsiveness to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning-and-memory mutant (displaying reduced response to the conditioned stimulus). These findings highlight the utility of a set of behavioral tasks used in a high-throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.