Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.
Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.
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DOI：
10.3389/fphys.2015.00324
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发表时间：
2015
影响因子：
4
通讯作者：
Maudsley S
中科院分区：
文献类型：
--
作者：
Daimon CM;Jasien JM;Wood WH 3rd;Zhang Y;Becker KG;Silverman JL;Crawley JN;Martin B;Maudsley S
自闭症谱系障碍（ASD）是一种复杂的异质性神经发育障碍，病因不明，目前还没有治愈。先前的研究已经证明，黑色和棕褐色，短尾（BTBR）T+ Itpr 3 tf/J小鼠品系显示出具有ASD样特征的行为表型。BTBR T+ Itpr 3 tf/J小鼠（简称为BTBR）表现出社交功能缺陷、缺乏沟通能力和参与刻板行为。尽管广泛的行为表型表征，很少有人知道的基因和蛋白质负责提出的ASD样表型的BTBR小鼠模型。在这项研究中，我们采用生物信息学技术，以获得一个广泛的理解与ASD样表型在BTBR小鼠的转录组和蛋白质组的变化。我们发现，与C57 BL/6 J（B6）对照小鼠相比，BTBR小鼠中的许多基因和蛋白质发生了显著改变，如BDNF，Shank 3和ERK 1，这些基因和蛋白质与ASD的先前研究高度相关。此外，我们确定了与B6对照相比BTBR小鼠中改变的不同功能途径，这些途径先前已被证明在ASD的两种小鼠模型和一些人类临床人群中改变，并被认为是ASD的可能病因学机制，包括“轴突导向”和“肌动蛋白细胞骨架的调节”。此外，我们的大规模生物信息学方法还发现了一些以前未鉴定的基因和蛋白质与BTBR小鼠中的ASD表型相关，如Caskin 1，这表明生物信息学可能是一种发现ASD新治疗靶点的途径。因此，我们认为，知情的协同生物信息学应用程序的使用是一个宝贵的工具，阐明复杂的疾病，如ASD的病因。
Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including “axon guidance” and “regulation of actin cytoskeleton.” In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.