Chen Jingshan, Lipska Barbara K, Weinberger Daniel R
Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biol Psychiatry. 2006 Jun 15;59(12):1180-8. doi: 10.1016/j.biopsych.2006.02.024. Epub 2006 May 2.
Translation of human genetic mutations into genetic mouse models is an important strategy to study the pathogenesis of schizophrenia, identify potential drug targets, and test new drugs for new antipsychotic treatments. Although it is impossible to recapitulate the full spectrum of schizophrenia symptoms in animal models, hypothesis-driven genetic mouse models have been successful in reproducing several schizophrenia-like behaviors and uncovering the roles of specific genes in dopamine and glutamine neurotransmission systems in mediating schizophrenia-like behaviors. Recent discoveries of susceptibility genes for schizophrenia and recognition of cognitive dysfunction as a core feature of schizophrenia and a phenotype of susceptibility for schizophrenia offer opportunities to develop newer genetic mouse models based on susceptibility. This new generation of genetic mouse models could shed light on the etiology of schizophrenia and lead us to new hypotheses, novel diagnostic tools, and more effective therapy.
将人类基因突变转化为基因小鼠模型是研究精神分裂症发病机制、确定潜在药物靶点以及测试新型抗精神病药物的重要策略。尽管在动物模型中不可能重现精神分裂症症状的全貌，但基于假设的基因小鼠模型已成功再现了几种类似精神分裂症的行为，并揭示了特定基因在多巴胺和谷氨酰胺神经传递系统中介导类似精神分裂症行为的作用。最近对精神分裂症易感基因的发现以及将认知功能障碍视为精神分裂症的核心特征和精神分裂症易感性表型，为开发基于易感性的新型基因小鼠模型提供了机会。这新一代基因小鼠模型可能会阐明精神分裂症的病因，并引导我们提出新的假设、开发新的诊断工具以及找到更有效的治疗方法。
