Ohl Frauke, Keck Martin E
Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804, Munich, Germany.
Eur J Pharmacol. 2003 Nov 7;480(1-3):219-28. doi: 10.1016/j.ejphar.2003.08.108.
Complementary to the 'gene-driven' analysis of gene function, 'phenotype-driven' approaches can be performed and may be equally important. Despite the current availability of a long list of mouse mutants, there remains an appreciable need for behavioural phenotypes in mouse models permitting to learn more about the aetiology of psychiatric disorders. This lack can be compensated by phenotype-driven ethyl-nitrosourea (ENU)-mutagenesis programs which aim at identifying novel phenotypes without any a priori assumptions, thus, representing a unique possibility to create novel animal models which approximate the underlying genetic aetiology. The power of mouse mutagenesis critically depends on the phenotyping procedures performed. In the case of ENU-mutants, behavioural phenotyping is especially challenging, as behavioural profiles have to be identified in single individuals. For high-throughput screening, approaches have been made to establish standardised screening protocols including a combination of well-validated, easy to perform behavioural tests. Different strategies are being introduced, which are used in ENU-mutagenesis screens to identify behavioural mutants representing possible endophenotypes of psychiatric diseases.
与基因功能的“基因驱动”分析相辅相成的是，可以采用“表型驱动”方法，而且这些方法可能同样重要。尽管目前已有一长串小鼠突变体，但对于小鼠模型中的行为表型仍有相当大的需求，以便更多地了解精神疾病的病因。表型驱动的乙基亚硝基脲（ENU）诱变程序可以弥补这一不足，该程序旨在在没有任何先验假设的情况下识别新的表型，因此，这是创建近似潜在遗传病因的新型动物模型的独特可能性。小鼠诱变的效果关键取决于所执行的表型分析程序。对于ENU突变体，行为表型分析尤其具有挑战性，因为必须在单个个体中识别行为特征。为了进行高通量筛选，已经采取措施建立标准化的筛选方案，包括组合经过充分验证且易于执行的行为测试。正在引入不同的策略，这些策略用于ENU诱变筛选，以识别代表精神疾病可能内表型的行为突变体。
