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

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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