IMPC: Disruption of PDZD8 as a potential cause of intellectual disability

智力障碍，也被称为智力低下，是一种终生疾病，损害个人的记忆、解决问题、语言和视觉理解以及自我照顾、独立和人际交流等日常生活技能。这种情况没有得到很好的治疗，部分原因是我们对大多数情况下的根本原因知之甚少。然而，我们确实知道智力残疾是可以遗传的，这表明可能与缺陷基因有关。这个项目将研究一种特殊的基因，PDZD8，我们最近发现它在一些智力残疾的人身上受到了破坏。要弄清楚有缺陷的PDZD8基因如何导致人类智力残疾，受到我们在人类受试者身上进行的研究的伦理限制的限制。但事实证明，一种实验室小鼠也有一个有缺陷的PDZD8基因，该基因模仿了一些ID患者的基因缺陷。因此，我们将使用这些PDZD8突变小鼠来尝试了解更多关于PDZD8在智力障碍中的作用，这可能为我们未来更好的治疗提供线索。行为测试是调查有缺陷的PDZD8基因和智力障碍之间的联系的最合适的方法，因为异常行为是这种疾病的主要症状。尽管小鼠不能完全复制人类的行为，但特别设计的测试可以检测出小鼠类似人类症状的行为异常。我们将使用这种方法来确定有缺陷的PDZD8基因对小鼠的行为影响。我们还将检查小鼠大脑的大小和形状是否异常。在这个为期一年的项目结束时，我们预计已经确定有缺陷的PDZD8基因是否会导致小鼠智力残疾相关的变化。如果PDZD8突变小鼠确实表现出类似智能障碍症状的异常，它们将被用于未来的研究，以进一步研究有缺陷的PDZD8基因如何影响大脑功能，并测试治疗这种疾病的新方法。

Intellectual disability, also known as mental retardation, is a life-long condition that impairs affected individuals' memory, problem solving, language and visual comprehension as well as daily living skills such as self-care, independence and interpersonal communication. The condition is poorly treated, in part because we know little about the root causes in most cases. However, we do know that intellectual disability can be inherited, suggesting that defective genes might be involved. This project will look at one particular gene, PDZD8, which we recently discovered to be damaged in some people with intellectual disability. Working out how the faulty PDZD8 gene might cause intellectual disability in people is constrained by ethical limitations on the studies that we can undertake on human subjects. But it turns out that a strain of laboratory mouse also has a faulty PDZD8 gene that mimics the gene defect in some ID patients. So we will use these PDZD8 mutant mice to try to learn more about the role of PDZD8 in intellectual disability, which might give us clues to better treatments in the future.Behavioural tests are the most appropriate for investigating the link between the faulty PDZD8 gene and intellectual disability because abnormal behaviours are the primary symptoms of the condition. Although mice do not fully replicate human behaviours, specially-designed tests can detect behavioural abnormalities in mice that resemble human symptoms. We will use this approach to identify the behavioural effects of the faulty PDZD8 gene in mice. We will also examine the mice for abnormalities in the size and shape of their brains.At the end of this 1-year project, we expect to have determined whether the faulty PDZD8 gene causes intellectual disability-related changes in the mice. If PDZD8 mutant mice do exhibit abnormalities resembling symptoms of intellectual disability, they will be used in future studies to further investigate how the faulty PDZD8 gene affects brain function, and to test new treatments for the condition.