Anatomical and functional consequences of dyslexia-gene DCDC2 knockout in a rat model

项目摘要/摘要 阅读障碍(DYS)是一种常见的发育障碍，具有很强的遗传成分，可 对学业和职业上的成功以及情感上的幸福都有重大影响。患有以下疾病的儿童 这种障碍的阅读分数比他们的年龄和年级至少低1个标准差 匹配的同龄人。尽管有这些诊断标准，但这里面有很大异质性 标签，既考虑到核心缺陷的严重性(S)，也考虑到 无序。这种异质性，再加上对这些机制缺乏深入的理解， 导致了一种一刀切的干预方法，而很大一部分人不这样做 对提供的干预选项做出回应。对人类的关联研究表明，阅读障碍- 易感基因DCDC2与大脑的解剖缺陷和任务缺陷有关 这需要速度。目前的研究将评估该基因是否与这些基因存在因果关系。 利用PI最近建立的一种新的基因敲除大鼠模型。如果确认这一点 基因确实会影响解剖学和快速听觉处理，这表明患有 携带该基因变异的阅读障碍可能会对针对这些基因的干预做出更有效的反应 特定的技能。

Project Summary/Abstract Dyslexia (DYS) is a common developmental disorder with a strong genetic component which can have a significant impact on academic and vocational success as well as emotional well-being. Children with this disorder have reading scores that are at least 1 standard deviation below their age- and grade- matched peers. In spite of these diagnostic criterion, there is a great deal of heterogeneity within this label, both with regard to the severity of the core deficit(s) as well as in the genetic basis of the disorder. This heterogeneity, combined with a lack of a strong understanding of these mechanisms, leads to a one-size-fits all approach to intervention and a significant portion of individuals do not respond to the intervention option offered. Association studies in humans suggest that the dyslexia- susceptibility gene DCDC2 is associated with anatomical deficits in the brain as well as deficits on tasks that require speed. The current studies will evaluate whether this gene is causally related to these deficits by utilizing a novel knockout rat model recently developed by the PI. If it is confirmed that this gene does impact anatomy and rapid auditory processing, it would suggest that individuals with dyslexia that carry a variant in this gene may respond more effectively to interventions targeting these specific skills.