Department of Physiology and Biophysics, State University of New York at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA.
Trends Neurosci. 2020 Nov;43(11):886-901. doi: 10.1016/j.tins.2020.09.001. Epub 2020 Sep 28.
Copy number variations (CNVs) of the human 16p11.2 genetic locus are associated with a range of neurodevelopmental disorders, including autism spectrum disorder, intellectual disability, and epilepsy. In this review, we delineate genetic information and diverse phenotypes in individuals with 16p11.2 CNVs, and synthesize preclinical findings from transgenic mouse models of 16p11.2 CNVs. Mice with 16p11.2 deletions or duplications recapitulate many core behavioral phenotypes, including social and cognitive deficits, and exhibit altered synaptic function across various brain areas. Mechanisms of transcriptional dysregulation and cortical maldevelopment are reviewed, along with potential therapeutic intervention strategies.
16p11.2 遗传位点的拷贝数变异 (CNVs) 与一系列神经发育障碍有关，包括自闭症谱系障碍、智力障碍和癫痫。在这篇综述中，我们描述了 16p11.2 CNVs 个体的遗传信息和多种表型，并综合了 16p11.2 CNVs 转基因小鼠模型的临床前发现。16p11.2 缺失或重复的小鼠重现了许多核心行为表型，包括社交和认知缺陷，并表现出各种脑区的突触功能改变。我们回顾了转录失调和皮质发育不良的机制，以及潜在的治疗干预策略。
