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Depletion of brain mitochondria cytochrome oxidase in the mottled mouse mutant
Abstract:
The mouse mutant Mobr is an animal model of Menkes kinky hair syndrome with a similar defect in copper utilization. The copper-dependent enzyme, cytochrome oxidase from the brain, liver, and heart mitochondria was examined. The brain and heart from Mobr/y had significantly less cytochrome alpha + alpha 3 than normal animals' when the cytochrome absorption spectra of tissue samples from animals 11 to 13 days of age were analyzed. Liver cytochrome was not significantly different. When brain mitochondrial cytochrome oxidase spectrograms from animals of different ages were examined, a major change was found to occur during the 2nd week of life. When cytochrome oxidase activity from brain mitochondria was measured, assaying the rate of oxidation of cytochrome c, the results were similar to those from spectrogram analysis.
Insights
The Mobr mouse model of Menkes kinky hair syndrome shows reduced cytochrome oxidase in the brain and heart, indicating impaired copper utilization. This defect significantly impacts copper-dependent enzymes during early development.
Area of Science:
- Biochemistry
- Neuroscience
- Genetics
Background:
- Menkes kinky hair syndrome is a genetic disorder affecting copper metabolism.
- The Mobr mouse mutant serves as an animal model for Menkes syndrome.
- Copper is essential for the function of various enzymes, including cytochrome oxidase.
Purpose of the Study:
- To investigate copper utilization defects in the Mobr mouse model.
- To examine the levels and activity of cytochrome oxidase in different tissues of Mobr mice.
- To determine the developmental timeline of cytochrome oxidase alterations in the Mobr model.
Main Methods:
- Analysis of cytochrome absorption spectra in brain, liver, and heart mitochondria.
- Spectroscopic examination of brain mitochondrial cytochrome oxidase across different ages.
- Measurement of cytochrome oxidase activity by assaying cytochrome c oxidation rates.
Main Results:
- Significantly lower levels of cytochrome alpha + alpha 3 were found in the brain and heart of Mobr/y mice compared to controls.
- Liver cytochrome levels did not show significant differences.
- A critical developmental change in brain mitochondrial cytochrome oxidase occurred during the second week of life.
Conclusions:
- The Mobr mouse model exhibits impaired copper utilization, specifically affecting cytochrome oxidase in the brain and heart.
- These findings highlight a critical developmental window for copper-dependent enzyme dysfunction in Menkes syndrome models.
- The study validates the Mobr mouse as a relevant model for studying Menkes kinky hair syndrome pathophysiology.