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

大鼠模型中阅读障碍基因 DCDC2 敲除的解剖学和功能后果

基本信息

批准号：
10623448
负责人：
Brenton G. Cooper
金额：
$ 4.72万
依托单位：
TEXAS CHRISTIAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10623448
关键词：
Affect Age Anatomy Auditory Auditory area Behavioral Brain Brain region Cells Cerebellum Child Complex Corpus striatum structure Development Discrimination Disease Dyslexia Ethical Issues Excision Exhibits Future Gene Expression Gene Targeting Genes Genetic Genetic Heterogeneity Goals Heterogeneity Homologous Gene Human Impairment Individual Intervention Knock-out Label Link Measurement Modeling Neurobiology Neuronal Plasticity Performance Phenotype Population Process Psychometrics Rattus Reading Research Rodent Rodent Model Role Severities Speech Discrimination Speech Sound Speed Susceptibility Gene Testing Training Variant Well in self Work auditory processing base behavioral impairment brain behavior causal variant developmental disease diagnostic criteria genetic testing gray matter in utero insight novel peer processing speed response skills sound success white matter

项目摘要

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.

项目概要/摘要阅读障碍 (DYS) 是一种常见的发育障碍，具有很强的遗传因素，可能会导致对学业和职业成功以及情感健康产生重大影响。儿童有这种疾病的阅读成绩至少比其年龄和年级低 1 个标准差匹配的同行。尽管有这些诊断标准，但其中仍存在很大的异质性标签，既涉及核心缺陷的严重程度，也涉及该缺陷的遗传基础紊乱。这种异质性，加上缺乏对这些机制的深刻理解，导致一种一刀切的干预方法，而很大一部分人不这样做回应所提供的干预选项。人类关联研究表明，阅读障碍易感基因 DCDC2 与大脑解剖缺陷以及任务缺陷有关需要速度的。目前的研究将评估该基因是否与这些因素存在因果关系通过利用 PI 最近开发的新型基因敲除大鼠模型来弥补缺陷。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对针对这些基因的干预措施做出更有效的反应具体技能。