Karl Tim
Neuroscience Research Australia Randwick, NSW, Australia ; Schizophrenia Research Institute Darlinghurst, NSW, Australia ; School of Medical Sciences, University of New South Wales NSW, Australia.
Front Behav Neurosci. 2013 Aug 15;7:106. doi: 10.3389/fnbeh.2013.00106. eCollection 2013.
Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors. In recent years, an increasing number of researchers worldwide have started investigating the "two-hit hypothesis" of schizophrenia predicting that genetic and environmental risk factors (GxE) interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. This mini review will focus on recent advancements in the field made by challenging mutant and transgenic rodent models for the schizophrenia candidate gene neuregulin 1 (NRG1) with particular environmental factors. It will outline results obtained from mouse and rat models for various Nrg1 isoforms/isoform types (e.g., transmembrane domain Nrg1, Type II Nrg1), which have been exposed to different forms of stress (acute versus chronic, restraint versus social) and housing conditions (standard laboratory versus minimally enriched housing). These studies suggest Nrg1 as a prime candidate for GxE interactions in schizophrenia rodent models and that the use of rodent models will enable a better understanding of GxE interactions and the underlying mechanisms.
精神分裂症是一种多因素疾病，具有高遗传性和环境风险因素。近年来，全球越来越多的研究人员开始研究精神分裂症的“双打击假说”，该假说预测遗传和环境风险因素（基因与环境相互作用，GxE）会相互作用导致该疾病的发生。这项工作开始产生有价值的新动物模型，并揭示了对精神分裂症病理生理学的新见解。本综述将重点关注该领域的最新进展，这些进展是通过用特定环境因素挑战精神分裂症候选基因神经调节蛋白1（NRG1）的突变和转基因啮齿动物模型而取得的。它将概述从小鼠和大鼠模型中获得的结果，这些模型针对各种Nrg1亚型/亚型类型（例如，跨膜结构域Nrg1、II型Nrg1），它们暴露于不同形式的应激（急性与慢性、束缚与社交）和饲养条件（标准实验室饲养与最低限度丰富饲养）下。这些研究表明，Nrg1是精神分裂症啮齿动物模型中基因与环境相互作用的主要候选因素，并且使用啮齿动物模型将有助于更好地理解基因与环境的相互作用及其潜在机制。
