Golgi study on the homozygote (Ml/Ml) of macular mutant mouse.

The macular mutant mouse shows X-linked recessive inheritance and its hemizygote (Ml/y) is considered to be an appropriate model of Menkes kinky hair disease (MKHD). In this study the homozygote (Ml/Ml) was bred by coupling CuCl2-treated Ml/y with Ml/+ and was clinically and neuropathologically examined. The Ml/Ml had white fur color and curly whiskers from day 3, showed ataxia and tonic seizure on day 8 and gradually lost weight after day 10. It died with severe emaciation around day 15. These clinical features were improved by CuCl2 injection. Quantitative analysis showed that the dendritic arborization of the pyramidal cell in the treated Ml/Ml was delayed on days 14, 20, 30, 45 and 90 in comparison with that of the age-matched +/y. In the cerebellum of the Ml/Ml on day 14, some of the Purkinje cells showed abnormal changes such as somal sprouts, spine-like structures on the surface of the soma and stem dendrites, thick stem dendrites, multiple focal swellings of the stem and distal dendrites, reduction in the size of dendritic trees and axonal focal swellings. These changes were gradually improved in the Ml/Ml with CuCl2 treatment after day 20, with the exception of the multiple focal swellings of the stem and distal dendrites. The dendritic focal swelling gradually decreased after day 45. These clinical and neuropathological features of the Ml/Ml are almost same as those of the Ml/y. In our mutant mouse, when the treated Ml/Ml is coupled with the treated Ml/y all offspring from the Ml/Ml are genetically Ml/y or Ml/Ml. Our study indicates that these fetal mice may be useful for studying the pathological and biochemical condition of prenatal MKHD.