Changes of copper level and cytochrome c oxidase activity in the macular mouse with age

The macular mouse is an animal model of Menkes disease. The neurological degeneration is caused by decreased cuproenzymes activity, such as cytochrome c oxidase (CCO), associated with copper deficiency in the brain. We investigated the age-related changes in copper concentration and CCO activity in the brain of macular mice which were given a single injection of cupric chloride on postnatal day 7. The copper concentration in the brain of macular mice was always about 40% of that of the age-matched controls. However, the copper concentration of both macular and control mice increased with age gradually. The CCO activity in the brain of macular mice was significantly lower than that of controls at the age of 8 days. However the activity in macular mice increased with growth and reached a level equal to the controls at 180 days. These results suggest that the improvement of CCO activity in the brain of macular mice is due to the brain copper concentration which increased with age. Therefore, parenteral administration of copper is recommended especially during infancy in patients with Menkes disease.