Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
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神经1α基因敲除小鼠的社交行为改变类似于神经发育障碍中的核心症状。
DOI：
10.1371/journal.pone.0067114
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fernandes C
中科院分区：
文献类型：
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作者：
Grayton HM;Missler M;Collier DA;Fernandes C
拷贝数变异已成为常见的、复杂的神经发育障碍的重要基因组原因。这些通常会改变多个基因的拷贝数，但与自闭症、精神分裂症和精神发育迟滞相关的2p16.3缺失只影响neurexin 1基因，通常是α亚型。先前对neurexin 1α（Nrxn 1 α）敲除（KO）小鼠作为这些疾病模型的分析揭示了突触传递的损伤，但未能揭示社会行为的缺陷，这是自闭症的核心症状之一。我们对纯遗传背景（C57 BL/6 J）小鼠中Nrxn 1 α缺失的行为影响进行了详细研究，以更好地了解其在神经发育障碍中的作用。在一系列行为试验中对野生型、杂合子和纯合子Nrxn 1 α KO雄性和雌性小鼠进行了试验（n = 9-16/基因型/性别）。 在纯合子Nrxn 1 α KO小鼠中，我们观察到改变的社会方法，减少社会调查，并减少在新环境中的运动活动。此外，雄性Nrxn 1 α KO小鼠表现出攻击行为增加。这是第一个将Nrxn 1 α的缺失与小鼠社会行为改变联系起来的实验数据。由于这代表了人类自闭症谱系障碍和精神分裂症中受影响的核心症状领域之一，我们的研究结果表明，在患者中发现的NRXN 1内的缺失可能是造成社会行为障碍的原因，并且Nrxn 1 α KO小鼠是人类神经发育障碍的有用模型。
Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α) knockout (KO) mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism. We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J) to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9–16 per genotype, per sex). In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours. These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder.
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影响因子：
--
作者：
Gregor A;Albrecht B;Bader I;Bijlsma EK;Ekici AB;Engels H;Hackmann K;Horn D;Hoyer J;Klapecki J;Kohlhase J;Maystadt I;Nagl S;Prott E;Tinschert S;Ullmann R;Wohlleber E;Woods G;Reis A;Rauch A;Zweier C
通讯作者：
Zweier C
DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin
影响因子：
4.7
作者：
Easton, Alanna C.;Lucchesi, Walter;Fernandes, Cathy
通讯作者：
Fernandes, Cathy
影响因子：
2.9
作者：
Lad, Heena Vanmalibhai;Liu, Lin;Schalkwyk, Leonard Cornelis
通讯作者：
Schalkwyk, Leonard Cornelis
影响因子：
15.9
作者：
Gerlai, R
通讯作者：
Gerlai, R