Department of Physiology and Cellular Biophysics, College of Physicians & Surgeons, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Neuroscience. 2012 Jun 1;211:136-64. doi: 10.1016/j.neuroscience.2011.07.051. Epub 2011 Jul 27.
Schizophrenia is one of the most common psychiatric disorders, but despite progress in identifying the genetic factors implicated in its development, the mechanisms underlying its etiology and pathogenesis remain poorly understood. Development of mouse models is critical for expanding our understanding of the causes of schizophrenia. However, translation of disease pathology into mouse models has proven to be challenging, primarily due to the complex genetic architecture of schizophrenia and the difficulties in the re-creation of susceptibility alleles in the mouse genome. In this review we highlight current research on models of major susceptibility loci and the information accrued from their analysis. We describe and compare the different approaches that are necessitated by diverse susceptibility alleles, and discuss their advantages and drawbacks. Finally, we discuss emerging mouse models, such as second-generation pathophysiology models based on innovative approaches that are facilitated by the information gathered from the current genetic mouse models.
精神分裂症是最常见的精神障碍之一，但尽管在确定与该病发展相关的遗传因素方面取得了进展，但该病的病因和发病机制仍知之甚少。开发小鼠模型对于加深我们对精神分裂症病因的理解至关重要。然而，将疾病病理学转化为小鼠模型一直具有挑战性，主要是因为精神分裂症的遗传结构复杂，以及在小鼠基因组中重现易感性等位基因的困难。在这篇综述中，我们重点介绍了主要易感性基因座模型的当前研究以及从其分析中获得的信息。我们描述并比较了不同易感性等位基因所必需的不同方法，并讨论了它们的优缺点。最后，我们讨论了新兴的小鼠模型，例如基于创新方法的第二代病理生理学模型，这些模型得益于从当前遗传小鼠模型中收集的信息。
