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

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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.