Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors.
Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors.
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DOI：
10.1038/s42003-021-02282-z
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发表时间：
2021-06-18
影响因子：
5.9
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Gao Y;Duque-Wilckens N;Aljazi MB;Wu Y;Moeser AJ;Mias GI;Robison AJ;He J
自闭症谱系障碍（ASD）是一种与多种基因突变相关的神经发育疾病。最近的遗传学和临床研究报道，表观遗传基因ASH1L突变与人类ASD和智力残疾（ID）高度相关。然而，将ASH1L突变与ASD/ID的发生联系起来的因果关系和潜在的分子机制仍未确定。本研究表明，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。基因表达分析揭示了ASH1L在神经细胞发育过程中调控基因表达的关键作用。因此，我们的研究建立了ASD/ID小鼠模型，揭示了表观遗传因子ASH1L在正常大脑发育中的关键功能，ASH1L突变与小鼠ASD/ID样行为之间的因果关系，以及ASH1L突变与脑功能异常之间的潜在分子机制。yuan Gao等人描述了小鼠大脑发育过程中组蛋白甲基转移酶（ASH1L）基因消融后脑形态、行为和基因表达的缺陷。他们的研究结果为ASH1L活性与神经发育障碍之间的联系提供了新的见解。
Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities. Yuen Gao et al. characterize deficits in brain morphology, behavior, and gene expression following genetic ablation of the histone methyltransferase, ASH1L, during brain development in mice. Their results provide new insight into links between ASH1L activity and neurodevelopmental disorders.
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FOXG1 综合征的核心表型包括出生后小头畸形、严重智力低下、语言缺失、运动障碍和胼胝体发育不全。
影响因子：
4
作者：
Kortüm F;Das S;Flindt M;Morris-Rosendahl DJ;Stefanova I;Goldstein A;Horn D;Klopocki E;Kluger G;Martin P;Rauch A;Roumer A;Saitta S;Walsh LE;Wieczorek D;Uyanik G;Kutsche K;Dobyns WB
通讯作者：
Dobyns WB
影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
DOI：
10.1007/978-1-62703-128-8_30
发表时间：
2013-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Louis, Sharon A;Mak, Carmen K H;Reynolds, Brent A
通讯作者：
Reynolds, Brent A
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
影响因子：
10.6
作者：
Schoch, Hannah;Kreibich, Arati S.;Ferri, Sarah L.;White, Rachel S.;Bohorquez, Dominique;Banerjee, Anamika;Port, Russell G.;Dow, Holly C.;Cordero, Lucero;Pallathra, Ashley A.;Kim, Hyong;Li, Hongzhe;Bilker, Warren B.;Hirano, Shinji;Schultz, Robert T.;Borgmann-Winter, Karin;Hahn, Chang-Gyu;Feldmeyer, Dirk;Carlson, Gregory C.;Abel, Ted;Brodkin, Edward S.
通讯作者：
Brodkin, Edward S.