RNA-seq transcriptional profiling in whole hippocampus in WT and Arid1b+/- mice

There is growing evidence for the involvement of ARID1B, a SWI/SNF ATP-dependent chromatin remodeling subunit, in a broad range of human disorders. Sequencing studies have recurrently implicated ARID1B haploinsufficiency in autism spectrum disorder (ASD), non-syndromic intellectual disability (ID), corpus callosum agenesis, and short stature. In addition, ARID1B is by far the most common cause of Coffin-Siris Syndrome (CSS), a monogenic developmental delay syndrome characterized by a combination of the neuropsychiatric and physical abnormalities mentioned above. To understand how ARID1B mutations lead to these phenotypes, we generated Arid1b mutant mice, which exhibited physical manifestations of developmental delay and behaviors reminiscent of ASD. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF- regulated genes implicated in ASD. WT and Arid1b+/- hippocampus at P80越来越多的证据表明，ARID1B是一种SWI/SNF ATP依赖型染色质重塑亚基（SWI/SNF ATP-dependent chromatin remodeling subunit），广泛参与人类多种疾病的病理过程。测序研究反复证实，ARID1B单倍剂量不足与自闭症谱系障碍（ASD）、非综合征性智力障碍（ID）、胼胝体发育不全及身材矮小密切相关。此外，ARID1B是目前已知的科芬-西里综合征（CSS）最常见的致病原因——该病是一类以所述神经精神与躯体异常组合为特征的单基因性发育迟缓综合征。为阐明ARID1B突变如何诱发上述表型，我们构建了Arid1b突变小鼠模型，该模型展现出发育迟缓的躯体表现以及类自闭症谱系障碍的行为特征。在脑组织中，Arid1b单倍剂量不足会导致与自闭症谱系障碍相关的SWI/SNF调控基因的表达发生改变。本研究的实验样本为出生后第80天（P80）的野生型（WT）与Arid1b+/-小鼠海马体。