Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental diseases associated with various gene mutations. Previous genetic and clinical studies reported that ASH1L is a high ASD risk gene identified in human patients. Our recent study used a mouse model to demonstrate that loss of ASH1L in the developing mouse brain was sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory, suggesting that the disruptive ASH1L mutations are the causative drivers leading the human ASD/ID genesis. Using this Ash1L-deletion-induced ASD/ID mouse model, here we showed that postnatal administration of vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), significantly ameliorated both ASD-like behaviors and ID-like cognitive memory deficit. Thus, our study demonstrates that SAHA is a promising reagent for the pharmacological treatment of core ASD/ID behavioral and memory deficits caused by disruptive ASH1L mutations.

自闭症谱系障碍（ASD）和智力障碍（ID）是与各种基因突变相关的神经发育疾病。先前的遗传和临床研究报告称， ASH1L是在人类患者中发现的 ASD 高风险基因。我们最近的研究使用小鼠模型证明，发育中的小鼠大脑中 ASH1L 的缺失足以导致多种发育缺陷、核心自闭症样行为和认知记忆受损，这表明破坏性ASH1L突变是导致人类ASD/ID 起源。使用Ash1L缺失诱导的 ASD/ID 小鼠模型，我们发现出生后给予组蛋白脱乙酰酶抑制剂 (HDACi) 伏立诺他 (SAHA) 可显着改善 ASD 样行为和 ID 样认知记忆缺陷。因此，我们的研究表明，SAHA 是一种很有前途的试剂，用于药物治疗由破坏性ASH1L突变引起的核心 ASD/ID 行为和记忆缺陷。