Takao Keizo, Yamasaki Nobuyuki, Miyakawa Tsuyoshi
Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Neurosci Res. 2007 Jun;58(2):124-32. doi: 10.1016/j.neures.2007.02.009. Epub 2007 Feb 20.
Despite massive research efforts, the exact pathogenesis and pathophysiology of psychiatric disorders, such as schizophrenia and bipolar disorder, remain largely unknown. Animal models can serve as essential tools for investigating the etiology and treatment of such disorders. Since the introduction of gene targeting techniques, the functions of more than 10% of all known mouse genes have been investigated by creating mutant mice. Some of these mutant mouse strains were found to exhibit behavioral abnormalities reminiscent of human psychiatric disorders. In this review, we discuss the general requirements for animal models of human psychiatric disorders. We also outline our unique approach of extrapolating findings in mice to humans, and present studies on forebrain-specific calcineurin knockout mice as an example. We also discuss the impact of a large-scale mouse phenotyping on studies of psychiatric disorders and the potential utility of an "animal-model-array" of psychiatric disorders for the development of suitable therapeutic agents.
尽管进行了大量研究，但精神分裂症和双相情感障碍等精神疾病的确切发病机制和病理生理学在很大程度上仍然未知。动物模型可作为研究此类疾病病因和治疗方法的重要工具。自从引入基因靶向技术以来，通过创建突变小鼠，已经对所有已知小鼠基因中超过10%的功能进行了研究。其中一些突变小鼠品系被发现表现出类似于人类精神疾病的行为异常。在这篇综述中，我们讨论了人类精神疾病动物模型的一般要求。我们还概述了将小鼠研究结果外推至人类的独特方法，并以大脑前叶特异性钙调神经磷酸酶基因敲除小鼠的研究为例进行介绍。我们还讨论了大规模小鼠表型分析对精神疾病研究的影响，以及精神疾病“动物模型阵列”在开发合适治疗药物方面的潜在用途。
