Department of Psychology, Colby College, Waterville, Maine, USA.
Genes Brain Behav. 2022 Jan;21(1):e12741. doi: 10.1111/gbb.12741. Epub 2021 Jun 21.
Mutations in the disrupted in schizophrenia-1 (DISC1) gene are associated with an increased risk of developing psychological disorders including schizophrenia, bipolar disorder, and depression. Assessing the impact of knocking out genes, like DISC1, in animal models provides valuable insights into the relationship between the gene and behavioral outcomes. Previous research has relied on mouse models to assess these impacts, however these may not yield as reliable or rich a behavioral analysis as can be obtained using rats. Thus, the goal of the present study was to characterize the behavioral effects of a biallelic functional deletion of the DISC1 gene in the Sprague Dawley rat. Female and male wild type and DISC1 knockout rats were assessed beginning just prior to weaning and during the post-weaning periadolescent period. The primary outcomes evaluated were activity, anxiety, responses to novel objects and conspecifics, and prepulse inhibition. These behaviors were selected as analogous indices of psychological dysfunction in humans. The DISC1 knockout had significant effects on behavior, although the kind and magnitude of deficits was different for females and males: in females, effects included hyperactivity, aversion to novelty, and a modest prepulse inhibition deficit; in males, effects in anxiety and neophobia were mild but their prepulse inhibition deficit was large. These data confirm that the DISC1 knockout rat model is an excellent way to reproduce and study symptoms of psychological disorders and provides compelling evidence for differential consequences of its dysfunction for females and males in the progression and emergence of specific behavioral deficits.
精神分裂症相关蛋白 1（DISC1）基因突变与多种心理障碍的风险增加有关，包括精神分裂症、双相情感障碍和抑郁症。评估基因（如 DISC1）在动物模型中的敲除效应为研究基因与行为结果之间的关系提供了有价值的见解。以前的研究依赖于小鼠模型来评估这些影响，但这些模型可能无法提供与大鼠模型一样可靠或丰富的行为分析。因此，本研究的目的是描述 Sprague Dawley 大鼠中 DISC1 基因双等位基因功能缺失的行为影响。在断奶前和断奶后青春期期间，对雌性和雄性野生型和 DISC1 敲除大鼠进行评估。评估的主要结果是活动、焦虑、对新物体和同种动物的反应以及前脉冲抑制。这些行为被选为人类心理功能障碍的类似指标。DISC1 敲除对行为有显著影响，但对雌性和雄性的影响类型和程度不同：在雌性中，影响包括过度活跃、对新奇事物的厌恶和适度的前脉冲抑制缺陷；在雄性中，焦虑和新事物恐惧症的影响较轻，但前脉冲抑制缺陷较大。这些数据证实，DISC1 敲除大鼠模型是复制和研究心理障碍症状的极好方法，并为其功能障碍对女性和男性在特定行为缺陷的进展和出现中的不同后果提供了有力证据。
