Reduced exploration, increased anxiety, and altered social behavior: Autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice
Reduced exploration, increased anxiety, and altered social behavior: Autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice
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DOI：
10.1016/j.bbr.2009.11.008
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发表时间：
2010-03-17
影响因子：
2.7
通讯作者：
Van der Zee, Catharina E. E. M.
中科院分区：
文献类型：
--
作者：
Balemans, Monique C. M.;Huibers, Marlon M. H.;Van der Zee, Catharina E. E. M.
9q34.3亚端粒缺失综合征（9q34.3subtelomericdeletionsyndrome，9q34.3subtelomericdeletionsyndrome，9q34.3subtelomericdeletionsyndrome，9q34.3subtelomericdeletionsyndrome）是由常染色质组蛋白甲基转移酶1（EI-IMT 1）基因单倍体缺失引起的一种新的智力低下综合征。患者还具有儿童张力减退、面部畸形、达到发育里程碑的延迟以及行为问题，如攻击性爆发、活动减退或自闭症样特征。使用雄性和雌性杂合Ehmt 1敲除小鼠（Ehmt 1（+/-），1-20个月大，保持在C57 BL/6 J背景下），通过将它们的行为与野生型同窝仔进行比较来研究它们是否模仿患者的行为特征。Ehmt 1（+/-）小鼠在暴露于开阔地、物体探索、大理石掩埋、明暗箱、镜室和T迷宫测试中的新环境时，与野生型小鼠相比，表现出活动和探索减少，焦虑增加。当遇到来自不同窝的老鼠时，他们也表现出减少的社会游戏，当接触到陌生老鼠时，他们对社会新奇感的反应延迟或缺失。然而，在Ehmt 1（+/-）和野生型小鼠之间没有观察到表型家笼运动活动或转棒运动功能的差异。总之，这些结果表明，在Ehmt 1（+/-）小鼠模型中重现了9q34.3亚端粒缺失综合征患者的活动减退和自闭症样特征，并且活动减退显然不是由任何运动功能障碍引起的。总之，这些观察结果使Ehmt 1（+/-）小鼠是9q34.3亚端粒缺失综合征患者自闭症样行为特征的可靠哺乳动物模型变得合理。(C)2009爱思唯尔有限公司版权所有。
The 9q34.3 subtelomeric deletion syndrome is a newly defined mental retardation syndrome, Caused by haplo-insufficiency of the euchromatin histone methyltransferase 1 (EI-IMT1) gene. Patients also have childhood hypotonia, facial dysmorphisms, delay in reaching developmental milestones, and behavioral problems like aggressive outbursts, hypoactivity, or autistic-like features. Male and female heterozygous Ehmt1 knockout mice (Ehmt1(+/-), aged 1-20 months, kept on a C57BL/6J background), were used to investigate whether they mimic the patients behavioral characteristics by comparing their behavior to wildtype littermates. The Ehmt1(+/-) mice revealed reduced activity and exploration, with increased anxiety-compared to wildtype mice when exposed to novel environments in the open field, object exploration, marble burying, light-dark box, mirrored chamber and T-maze tests. They also demonstrated diminished social play when encountering a mouse from a different litter, and a delayed or absent response to social novelty when exposed to a stranger mouse. However, no differences in phenotyper home cage locomotor activity or rotarod motor function were observed between Ehmt1(+/-) and wildtype mice. Together, these results indicate that the hypoactivity and the autistic-like features of 9q34.3 subtelomeric deletion syndrome patients are recapitulated in this Ehmt1(+/-) mouse model, and that the hypoactivity is apparently not caused by any motor dysfunction. Together, these observations make it plausible that the Ehmt1(+/-) mouse is a faithful mammalian model for the autistic-like behavioral features of patients with the 9q34.3 subtelomeric deletion syndrome. (C) 2009 Elsevier B.V. All rights reserved.