Investigating the functional impact of SHANK2 mutations in differentiated human induced pluripotent stem cells as a model for neurodevelopmental disorders

研究 SHANK2 突变对分化人类诱导多能干细胞作为神经发育障碍模型的功能影响

• 批准号: 407247919
• 负责人: Dr. Simone Berkel
• 金额: --
• 依托单位: Abteilung für Molekulare Humangenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/407247919?language=en
• 关键词: Investigating; functional; impact; SHANK2; mutations

To gain novel insight into the pathogenesis of neurodevelopmental disorders such as intellectual disability and autism, we plan to analyze the functional impact of SHANK2 mutations in differentiated human induced pluripotent stem cells. SHANK2 encodes for a postsynaptic scaffolding protein at glutamatergic synapses in the brain, which plays a central role in synapse formation, maintenance and function. To date, several patients with intellectual disability and autism have been identified with SHANK2 de novo mutations. Investigating the impact of different SHANK2 mutations on neuronal differentiation, synapse formation and general neuronal function, will elucidate the role of SHANK2 during early human neuronal development and will help to identify the molecular and cellular alterations in individuals with SHANK2 deletions. The improved understanding of the pathogenesis of autism and intellectual disability gained by this study can be used for the development of pharmacological intervention strategies.

为了获得对智力障碍和自闭症等神经发育障碍的发病机制的新见解，我们计划分析 SHANK2 突变对分化的人类诱导多能干细胞的功能影响。 SHANK2 编码大脑谷氨酸突触的突触后支架蛋白，在突触形成、维持和功能中发挥核心作用。迄今为止，几名智力障碍和自闭症患者已被确定患有 SHANK2 新突变。研究不同 SHANK2 突变对神经元分化、突触形成和一般神经元功能的影响，将阐明 SHANK2 在人类早期神经元发育过程中的作用，并有助于识别 SHANK2 缺失个体的分子和细胞改变。这项研究加深了对自闭症和智力障碍发病机制的了解，可用于制定药物干预策略。