High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder.
High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder.
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DOI：
10.1371/journal.pone.0109872
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Poptani H
中科院分区：
文献类型：
--
作者：
Kumar M;Duda JT;Hwang WT;Kenworthy C;Ittyerah R;Pickup S;Brodkin ES;Gee JC;Abel T;Poptani H
自闭症谱系障碍（ASD）包括一组病因异质性神经发育障碍。神经连接素-3（NL-3）是一种细胞粘附蛋白，介导突触发育，并与ASD有关。我们在3个不同的时间点（30、50和70日龄）对NL-3和野生型同窝仔进行了离体高分辨率磁共振成像（MRI），包括扩散张量成像（DTI）和行为（社交方法和零迷宫）测试，以评估NL-3小鼠的发育脑异常。MRI数据被分割成39个不同的灰质和白色物质区域。体积测量，沿着与DTI指数从这些分割的区域也进行了。在控制年龄和性别后，NL-3基因敲入动物与其野生型同窝仔相比表现出显著降低的社交性和较低的焦虑相关行为。在考虑年龄、性别和时间点作为协变量后，还观察到NL-3基因敲入小鼠中几个白色和灰质区域的体积显著减少。这些发现表明，NL-3小鼠大脑的结构变化是由NL-3基因突变引起的。没有观察到显着差异的DTI指数，这表明NL-3突变可能不会有深刻的影响水扩散检测DTI。容积和DTI研究有助于理解ASD风险模型上的破坏功能的生物学，并可能有助于开发ASD的成像生物标志物。
Autism spectrum disorders (ASD) comprise an etiologically heterogeneous set of neurodevelopmental disorders. Neuroligin-3 (NL-3) is a cell adhesion protein that mediates synapse development and has been implicated in ASD. We performed ex-vivo high resolution magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and behavioral (social approach and zero maze) tests at 3 different time points (30, 50 and 70 days-of-age) on NL-3 and wild-type littermates to assess developmental brain abnormalities in NL-3 mice. MRI data were segmented in 39 different gray and white matter regions. Volumetric measurements, along with DTI indices from these segmented regions were also performed. After controlling for age and gender, the NL-3 knock-in animals demonstrated significantly reduced sociability and lower anxiety-related behavior in comparison to their wild type littermates. Significantly reduced volume of several white and gray matter regions in the NL-3 knock-in mice were also observed after considering age, gender and time point as covariates. These findings suggest that structural changes in the brain of NL-3 mice are induced by the mutation in the NL-3 gene. No significant differences in DTI indices were observed, which suggests that the NL-3 mutation may not have a profound effect on water diffusion as detected by DTI. The volumetric and DTI studies aid in understanding the biology of disrupting function on an ASD risk model and may assist in the development of imaging biomarkers for ASD.
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