Brain Abnormalities in a Neuroligin3 R451C Knockin Mouse Model Associated With Autism
Brain Abnormalities in a Neuroligin3 R451C Knockin Mouse Model Associated With Autism
复制标题
DOI：
10.1002/aur.215
复制
发表时间：
2011-10-01
期刊：
影响因子：
4.7
通讯作者：
Henkelman, R. Mark
中科院分区：
文献类型：
--
作者：
Ellegood, Jacob;Lerch, Jason P.;Henkelman, R. Mark
磁共振成像（MRI）已被广泛用于检查人类和动物大脑的形态学变化。检查人类自闭症小鼠模型的许多优点之一是，我们能够检查单基因靶点，如Neuroligin 3 R451 C敲入（NL 3 KI），它直接涉及人类自闭症。NL 3 KI小鼠模型在脑中的许多不同结构中具有显著的体积差异：发现NL 3 KI中的灰质结构，例如海马体、纹状体和丘脑都较小。此外，发现许多白色结构明显较小，如大脑脚、胼胝体、穹窿/伞和内囊。分数各向异性测量在这些结构中也进行了测量，并没有发现差异，因此，体积的变化在白色物质区域，是不是由于一般的组织的微观结构中的故障，似乎是由较少的轴突或不成熟的轴突。在胼胝体和小脑的局部区域也发现了较大的径向扩散率。胼胝体的变化特别有趣，因为胼胝体变薄（或体积减小）是自闭症的一致发现。这表明，NL 3 KI模型可能有助于检查与自闭症相关的白色物质变化。Autism Res 2011，4：368-376. (C)2011年国际自闭症研究学会，Wiley Periodicals，Inc。
Magnetic resonance imaging (MRI) has been used quite extensively for examining morphological changes in human and animal brains. One of the many advantages to examining mouse models of human autism is that we are able to examine single gene targets, like that of Neuroligin3 R451C knockin (NL3 KI), which has been directly implicated in human autism. The NL3 KI mouse model has marked volume differences in many different structures in the brain: gray matter structures, such as the hippocampus, the striatum, and the thalamus, were all found to be smaller in the NL3 KI. Further, many white matter structures were found to be significantly smaller, such as the cerebral peduncle, corpus callosum, fornix/fimbria, and internal capsule. Fractional anisotropy measurements in these structures were also measured, and no differences were found. The volume changes in the white matter regions, therefore, are not due to a general breakdown in the microstructure of the tissue and seem to be caused by fewer axons or less mature axons. A larger radial diffusivity was also found in localized regions of the corpus callosum and cerebellum. The corpus callosal changes are particularly interesting as the thinning (or reduced volume) of the corpus callosum is a consistent finding in autism. This suggests that the NL3 KI model may be useful for examining white matter changes associated with autism. Autism Res 2011,4: 368-376. (C) 2011 International Society for Autism Research, Wiley Periodicals, Inc.