Electron microscopic study on the homozygote (Ml/Ml) of the macular mutant mouse

The macular mouse is a mutant mouse with a defect in copper transport and an X-linked recessive inheritance. Its hemizygote (Ml/y) is considered to be an appropriate model fo Menkes kinky hair disease (MKHD). In this study, homozygote (Ml/Ml) were bred by coupling CuCl2-treated Ml/y with heterozygote (Ml/+). Both Ml/Ml and Ml/y die around day 15 of age. However, treatment with CuCl2 enables them to live until adulthood. The brains of Ml/Ml were chronologically examined by light and electron microscopy. In the non-treated Ml/Ml, abnormal mitochondria increased in number in the cerebral cortical neurons and in the cerebellar Purkinje cells from day 7 to 14 of age. In the treated Ml/Ml, the administration of CuCl2 improved the abnormality of the mitochondria in the cerebrum by day 20, but those in the Purkinje cells remained until day 60. Flattened cisterns and intracytoplasmic inclusions were also observed in the Purkinje cells of treated Ml/Ml. These ultrastructural changes were quite similar to those observed in the Ml/y. Our mutant mice (treated Ml/Ml), when they are coupled with treated Ml/y, can give birth to offspring, all of which will be genetically Ml/y or Ml/Ml. These fetal mice will be very helpful for studying the pathological and biochemical condition of prenatal MKHD.