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

一种磁共振成像技术被开发出来，其中马鞍线圈被调整用于老鼠的大脑。该技术应用于具有髓鞘碱性蛋白（MBP）基因改变的shiverer突变小鼠。获取T1和T2加权图像，计算T1和T2映射。野生型小鼠和杂合突变型小鼠（MBPshi/+）在T2加权图像上胼胝体及胼胝体辐射均显示低强度信号。基底神经节也显示稍低的信号强度。另一方面，颤抖突变小鼠（MBPshi/MBPshi）的大脑皮层和白质的信号强度没有明显差异。对野生型、MBPshi/+和MBPshi/MBPshi小鼠胼胝体进行KB染色、抗mbp抗体免疫组化和电镜观察。野生型与MBPshi/+小鼠髓鞘染色无明显差异，髓鞘多层膜结构无明显差异。因此，只有一个异常MBP基因拷贝的MBPshi/+小鼠不能作为人类18q-综合征的有效模型。通过脑MRI和尸检对一个患有18号染色体环的男孩进行了研究。T2加权图像显示弥漫性高强度信号遍布脑白质。免疫组化检查显示脑白质KB和抗mbp染色均匀。电镜显示轴突簇被紧密的髓鞘包裹，有明显的主密线。以前认为T2加权MRI图像的高强度信号是由MBP基因异常引起的髓鞘发育异常引起的。我们的病理研究表明，大脑白质髓鞘发育良好，这与目前对18q综合征的认识有很大不同。我们展示了在评估这种突变小鼠作为有效动物模型时使用病理生理分析与MRI成像相结合的重要性。少

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