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Changes of copper level and cytochrome c oxidase activity in the macular mouse with age
1Department of Pediatrics, Teikyo University, School of Medicine, Tokyo, Japan.
Abstract:
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 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.
Insights
Parenteral copper administration in infancy may benefit Menkes disease patients. Macular mice showed improved cytochrome c oxidase (CCO) activity with age, linked to increased brain copper levels.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Menkes disease is a genetic disorder causing neurological degeneration due to copper deficiency.
- The macular mouse serves as an animal model for studying Menkes disease.
- Cuproenzymes, like cytochrome c oxidase (CCO), are vital for brain function and are affected by copper levels.
Purpose of the Study:
- To investigate age-related changes in brain copper concentration and CCO activity in macular mice.
- To assess the impact of early copper supplementation on neurological recovery in the macular mouse model.
- To establish a correlation between brain copper levels and CCO activity in the context of Menkes disease.
Main Methods:
- Macular mice received a single injection of cupric on postnatal day 7.
- Brain copper concentration was measured at various time points.
- Cytochrome c oxidase (CCO) activity in the brain was assessed.
- Age-matched control mice were used for comparison.
Main Results:
- Macular mice consistently showed approximately 40% lower brain copper concentration than controls.
- Both macular and control mice exhibited a gradual increase in brain copper with age.
- CCO activity was significantly lower in macular mice at 8 days but normalized by 180 days.
- The recovery of CCO activity correlated with increasing brain copper levels.
Conclusions:
- Increased brain copper concentration with age contributes to improved CCO activity in macular mice.
- Early parenteral copper administration is recommended for Menkes disease patients, particularly during infancy.
- The macular mouse model demonstrates potential for evaluating therapeutic strategies for Menkes disease.