权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Research on the pathophysiology of human dysmyelination using magnetic resonance imaging of a mutant mouse

利用突变小鼠的磁共振成像研究人类髓鞘形成障碍的病理生理学

基本信息

批准号：
15591084
负责人：
IWASAKI Nobuaki
金额：
$ 1.92万
依托单位：
Ibaraki Prefectural University of Healty Sciences (2004)University of Tsukuba (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

A magnetic resonance imaging technique was developed in which the saddle coil was adjusted for use on the mouse brain. This technique was applied to the shiverer mutant mouse, which has an altered myelin basic protein (MBP) gene. The T1 and T2 weighted images were acquired and T1 and T2 maps were calculated. In the wild-type mice and the heterozygous mutant mice (MBPshi/+), the corpus callosum and the radiation of the corpus callosum displayed low intensity signal on T2 weighted images. The basal ganglia also displayed slightly lower intensity signal. On the other hand, the shiverer mutant mice (MBPshi/MBPshi) did not show a clear difference between the signal intensities of the cerebral cortex and the white matter.Kluver-Barrera (KB) staining, immunohistochemistry with anti-MBP antibody and electron micrographs were performed on the corpus callosum of wild-type, MBPshi/+ and MBPshi/MBPshi mice. No difference in the myelin staining, nor in the multilamellar membrane structures of myeli … More n sheaths was revealed between the wild-type and the MBPshi/+ mice. Therefore, the MBPshi/+ mice with only one copy of the abnormal MBP gene were not found to be a valid model of human 18q- syndrome.A boy afflicted with chromosome 18 ring was investigated by brain MRI and autopsy examination. The T2 weighted image revealed diffuse high intensity signals throughout the cerebral white matter. Immunohistochemical examination showed uniform KB and anti-MBP staining of the cerebral white matter. Electron microscopy revealed clusters of axons wrapped by compacted myelin sheaths with distinct major dense lines. It has previously been assumed that the high intensity signal of T2 weighted MRI images was caused by dysmyelination resulting from the MBP gene abnormality. Our pathological study demonstrated that the cerebral white matter was well-myelinated, a result which is quite different from the current understanding of 18q-syndrome.We show the importance of using pathophysiological analysis in combination with MRI imaging in evaluating this mutant mouse as a valid animal model. Less

开发了一种磁共振成像技术，其中调整鞍形线圈以用于小鼠大脑。这项技术被应用于颤抖突变小鼠，它具有改变的髓鞘碱性蛋白（MBP）基因。获取T1和T2加权像，计算T1和T2图。野生型小鼠和杂合子突变小鼠（MBPshi/+）胼胝体和胼胝体放射线在T2加权像上显示低信号。基底神经节也显示稍低强度信号。另一方面，颤抖突变小鼠（MBPshi/MBPshi）大脑皮质和白色物质的信号强度之间没有明显的差异，对野生型、MBPshi/+和MBPshi/MBPshi小鼠的胼胝体进行了Kluver-Barrera（KB）染色、用抗MBP抗体进行的免疫组织化学和电子显微镜照片。髓鞘染色和髓鞘的多层膜结构无差异， ...更多信息在野生型和MBPshi/+小鼠之间显示出n鞘。因此，只有一个拷贝的异常MBP基因的MBPshi/+小鼠不能作为人类18 q-综合征的有效模型。T2加权像显示整个大脑白色物质弥漫性高强度信号。免疫组化显示脑内白色物质呈均匀的KB和抗MBP染色。电子显微镜下发现由致密髓鞘包裹的轴突簇，具有明显的主要致密线。先前已经假设T2加权MRI图像的高强度信号是由MBP基因异常导致的髓鞘形成障碍引起的。我们的病理学研究表明，大脑白色物质是良好的髓鞘，这是一个结果，这是从目前的理解18 q-syndrome.We显示的重要性，使用病理生理学分析结合MRI成像评估这种突变小鼠作为一个有效的动物模型。少