Neuropathological study on cerebellum of macular mutant mouse heterozygote.

The hemizygote of the macular mutant mouse is clinically, biochemically and neuropathologically similar to a patient with Menkes kinky hair disease. The heterozygote of this mutant mouse was biochemically and neuropathologically examined. The copper content in the brain decreased in comparison with that in the normal littermate, although it was more than that in the hemizygote. In the Golgi study, abnormal Purkinje cells with somal sprouts, thick stem dendrites and dendritic focal swellings, which were seen in the hemizygote, were not observed in the heterozygote. Ultrastructurally, abnormal mitochondria were seen in the Purkinje cells in the anterior and middle cerebellar lobe of the heterozygote. Histochemically, cytochrome c oxidase activity decreased, especially at the anterior lobe in the cerebellar cortex of the heterozygote. This activity, as indicated by staining intensity, was in between that in the normal littermate and that in the hemizygote. The heterozygote did not show a mosaic pattern in the distribution of these neuropathological changes, although this mutant mouse shows x-linked recessive inheritance. Thus, our results lead to the conclusion that the neuropathological changes observed in this mutant mouse do not result directly from an abnormal gene in the Purkinje cell, but from the secondary effects of subsequent to presumptive copper deficiency.