Transcriptional profiling of dorsal striatum in 1-year-old WT mice and Ash1l heterozygous mice

Ash1l encodes a histone methyltransferase, a member of the trithorax group proteins, which regulates developmental essential gene expression by catalyzing H3K36 methylation and counteracting polycomb silencing. Accumulating reports suggest the loss-of-function mutants in Ash1l gene are associated with intellectual disability (ID), attention-deficit/hyperactivity (ADHD), autism spectrum disorder (ASD), Tourette syndrome (TS) and multiple congenital anomalies (MCA). We performed transcriptional profiling of dorsal striatum in 1-year-old Ash1l mutant brain via RNA sequencing (RNA-seq). Ash1l haploinsufficiency induces transcription alternation of genes involved in synaptic function and cortical development, implicating the deficits in synapse pruning and behavior in adult mice. 3 WT (1-year-old) and 3 Ash1l heterozygous (1-year-old) dorsal striatumAsh1l 编码组蛋白甲基转移酶（histone methyltransferase），属于三胸族蛋白（trithorax group proteins）家族，可通过催化H3K36甲基化并拮抗多梳蛋白沉默（polycomb silencing）调控发育必需基因的表达。现有多项研究表明，Ash1l 基因的功能缺失突变与智力障碍（intellectual disability, ID）、注意缺陷多动障碍（attention-deficit/hyperactivity disorder, ADHD）、孤独症谱系障碍（autism spectrum disorder, ASD）、抽动秽语综合征（Tourette syndrome, TS）以及多发先天性畸形（multiple congenital anomalies, MCA）密切相关。本研究通过RNA测序（RNA-seq）技术，对1岁龄Ash1l突变小鼠大脑的背侧纹状体开展了转录组谱分析。Ash1l 单倍体剂量不足（haploinsufficiency）会引发参与突触功能与皮层发育的基因转录改变，提示成年小鼠存在突触修剪与行为缺陷。3只野生型（wild type, WT）1岁龄小鼠及3只Ash1l杂合子1岁龄小鼠的背侧纹状体