Oliver Peter L
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, U.K.
ScientificWorldJournal. 2011 Jul 7;11:1411-20. doi: 10.1100/tsw.2011.128.
The modelling of neuropsychiatric disease using the mouse has provided a wealth of information regarding the relationship between specific genetic lesions and behavioural endophenotypes. However, it is becoming increasingly apparent that synergy between genetic and nongenetic factors is a key feature of these disorders that must also be taken into account. With the inherent limitations of retrospective human studies, experiments in mice have begun to tackle this complex association, combining well-established behavioural paradigms and quantitative neuropathology with a range of environmental insults. The conclusions from this work have been varied, due in part to a lack of standardised methodology, although most have illustrated that phenotypes related to disorders such as schizophrenia are consistently modified. Far fewer studies, however, have attempted to generate a "two-hit" model, whereby the consequences of a pathogenic mutation are analysed in combination with environmental manipulation such as prenatal stress. This significant, yet relatively new, approach is beginning to produce valuable new models of neuropsychiatric disease. Focussing on prenatal and perinatal stress models of schizophrenia, this review discusses the current progress in this field, and highlights important issues regarding the interpretation and comparative analysis of such complex behavioural data.
利用小鼠对神经精神疾病进行建模，已经提供了大量有关特定基因损伤与行为内表型之间关系的信息。然而，越来越明显的是，遗传因素和非遗传因素之间的协同作用是这些疾病的一个关键特征，也必须予以考虑。鉴于回顾性人类研究存在固有限制，小鼠实验已开始着手解决这种复杂关联，将成熟的行为范式和定量神经病理学与一系列环境损伤因素相结合。这项工作得出的结论各不相同，部分原因是缺乏标准化方法，不过大多数研究都表明，与精神分裂症等疾病相关的表型会持续发生改变。然而，尝试构建“双打击”模型的研究要少得多，即在这种模型中，结合诸如产前应激等环境因素来分析致病突变的后果。这种重要但相对较新的方法正开始产生有价值的神经精神疾病新模型。本综述聚焦于精神分裂症的产前和围产期应激模型，讨论了该领域的当前进展，并强调了有关此类复杂行为数据的解释和比较分析的重要问题。
