The Effects of Neurexin-1 Deficiency on Behavioural Phenotypes Relevant to Schizophrenia and Autism Spectrum Disorder

Neurexin-1 缺乏对精神分裂症和自闭症谱系障碍相关行为表型的影响

• 批准号: G0900625/1
• 负责人: Steven Clapcote
• 金额: $ 28.08万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900625%2F1
• 关键词: Effects; Neurexin; Deficiency; Behavioural; Phenotypes

Autism spectrum disorders (ASDs) and schizophrenia are forms of mental illness that have profound, long-term impacts on the very many who will be affected in their lifetimes. Both conditions are poorly treated, in part because we know little about the root causes. However, we do know that these illnesses can be inherited, suggesting that defective genes might be involved. This project looks at one particular gene neurexin 1alpha, which was recently discovered to be damaged in some ASD and schizophrenia patients. Working out how the faulty neurexin 1alpha gene might predispose to ASD and schizophrenia is difficult because we can?t ever do the necessary studies in patients. But it turns out that a strain of laboratory mouse also has a faulty neurexin 1alpha gene that mimics the gene defect in patients. So we will use these neurexin 1alpha mutant mice to try to learn more about the role of neurexin 1alpha in ASD and schizophrenia, which might give us clues to better treatments and prevention strategies in the future.Behavioural tests are the most appropriate for investigating the link between the faulty neurexin 1alpha gene and ASD and schizophrenia because abnormal behaviours are the primary symptoms of both disorders. While mental illnesses cannot be replicated in mice, specially-designed behavioural tests can detect behavioural abnormalities in mice that resemble human psychiatric symptoms. We will use this approach to identify the behavioural effects of the faulty neurexin 1alpha gene in mice.At the end of this project, we expect to have identified the ASD- and schizophrenia-related behavioural changes caused by the faulty neurexin 1alpha in mice, generated evidence to help us understand the link between neurexin 1alpha gene defects and mental illness in humans, and determined whether neurexin 1alpha mutant mice exhibit a resemblance to symptoms of ASD or schizophrenia so that they can be used to investigate disease causes and novel treatments in future studies.

自闭症谱系障碍（ASDs）和精神分裂症是精神疾病的两种形式，对许多人在其一生中将受到影响的人产生深远的长期影响。这两种疾病都没有得到很好的治疗，部分原因是我们对其根本原因知之甚少。然而，我们确实知道这些疾病可以遗传，这表明可能涉及有缺陷的基因。这个项目着眼于一种特殊的基因neurexin 1alpha，该基因最近被发现在一些ASD和精神分裂症患者中受损。弄清楚有缺陷的神经素1 α基因是如何使人易患自闭症谱系障碍和精神分裂症的是很困难的，因为我们可以？我从未在病人身上做过必要的研究。但事实证明，一种实验室老鼠也有一个有缺陷的神经素1 α基因，它模仿了病人的基因缺陷。因此，我们将利用这些neurexin 1alpha突变小鼠，试图更多地了解neurexin 1alpha在ASD和精神分裂症中的作用，这可能为我们未来更好的治疗和预防策略提供线索。行为测试最适合用于研究神经素1 α基因缺陷与自闭症谱系障碍和精神分裂症之间的联系，因为异常行为是这两种疾病的主要症状。虽然精神疾病不能在老鼠身上复制，但专门设计的行为测试可以检测出老鼠身上类似人类精神症状的行为异常。我们将使用这种方法来确定有缺陷的neurexin 1alpha基因对小鼠的行为影响。在本项目结束时，我们期望能够在小鼠中识别出由neurexin 1alpha缺陷引起的ASD和精神分裂症相关的行为改变，产生证据来帮助我们理解neurexin 1alpha基因缺陷与人类精神疾病之间的联系，并确定neurexin 1alpha突变小鼠是否表现出与ASD或精神分裂症症状相似的症状，以便在未来的研究中用于研究疾病原因和新的治疗方法。