Transcriptome analysis of auditory cortex in 1-month-old and 1-year-old Ash1l heterozygous mice with their age-matched WT littermates

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 transcriptome analysis of auditory cortex in 1-month-old and 1-year-old Ash1l Ash1l heterozygous mice with their age-matched WT littermates 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-month-old) and 3 Ash1l heterozygous (1-month-old) auditory cortex;2 WT (1-year-old) and 2 Ash1l heterozygous (1-year-old) auditory cortexAsh1l 编码组蛋白甲基转移酶（histone methyltransferase），属于三胸族蛋白（trithorax group proteins）成员，可通过催化H3K36甲基化并拮抗多梳沉默（polycomb silencing）调控发育必需基因的表达。现有研究表明，Ash1l基因的功能丧失突变体与智力障碍（intellectual disability, ID）、注意缺陷多动障碍（attention-deficit/hyperactivity, ADHD）、孤独症谱系障碍（autism spectrum disorder, ASD）、抽动秽语综合征（Tourette syndrome, TS）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），对1月龄与1岁龄Ash1l杂合突变小鼠及其同窝野生型（WT）对照的听觉皮层开展转录组分析。结果显示，Ash1l单倍体剂量不足（haploinsufficiency）会诱导参与突触功能与皮层发育的基因转录发生改变，提示成年小鼠存在突触修剪缺陷与行为异常。本研究涉及的样本包括：3份1月龄野生型听觉皮层样本、3份1月龄Ash1l杂合突变听觉皮层样本；2份1岁龄野生型听觉皮层样本、2份1岁龄Ash1l杂合突变听觉皮层样本。