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.

中文翻译：

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雌性和雄性 DISC1 敲除大鼠青春期发育期间行为缺陷的进展不同

disruption in schizophrenia-1 (DISC1) 基因突变与精神分裂症、双相情感障碍和抑郁症等心理障碍的风险增加有关。在动物模型中评估敲除基因（如 DISC1）的影响，可以为基因与行为结果之间的关系提供有价值的见解。以前的研究依赖于小鼠模型来评估这些影响，但是这些可能无法像使用大鼠获得的那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。雌性和雄性野生型和 DISC1 基因敲除大鼠在断奶前和断奶后围青春期开始进行评估。评估的主要结果是活动、焦虑、对新物体和同种异物的反应，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 敲除对行为有显着影响，尽管女性和男性的缺陷类型和程度不同：在女性中，影响包括多动、厌恶新奇事物和适度的前脉冲抑制缺陷；在男性中，对焦虑和新恐惧症的影响是轻微的，但他们的前脉冲抑制缺陷很大。