Copper metabolism in the macular mutant mouse as an animal model of Menkes kinky hair disease

The copper,zinc and metallothionein contents were measurded in various tissues of mutant (hemizygous and homozygous) macular,heterozygous macular and normal mice.The copper contents in the kidney and small intestine of 7-day-old mutants and heterozygotes were much higher than in normal mice,whereas the copper contents in the other tissues (liver,brain spleen and serum) were low.Renal copper contents of 1-day-old mutants were not different from contents of normal mice,whereas those of 7-,and 14-day-old mutants were significantly elevated.Hepatic and brain copper contents were extremely low at all stages compared to normals.Copper therapy was applide to 7-day-old mutant mice.One day after injection,hepatic copper contents in mutants increased slightly compared to the normal controls,whereas renal copper contents increasded greatly.Seven days after injection,hepatic copper contents in mutants decreased greatly compared to the normal control,whereas the increase in renal copper contents remained.One and 7 days after injectin,brain copper contents in mutants and normal mice increasde slightly compared to untreated mice.The renal MT-Cu contents in 7-and 8-day-old mutants and heterozygotes were significantly greater than that of normal mice.The marked elevation in renal MT-Cu contents was also observed in 8-and 9-week-old mutants and heterozygotes. In contrast to the kidney,hepatic MT-Cu contents in 7-and 8-day-old mutants and heterozygotes were much lower than in normal mice.In contrast to copper,no significant differences in zinc levels in any tissue were evident.