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Electron microscopic study of optic nerves of macular mice
1Department of Ophthalmology, Nagasaki University School of Medicine, Japan.
Abstract:
The optic nerve of the macular mouse as a model of Menkes' disease was examined by electron microscopy. Since hemizygote macular mice die at 14 or 15 days of age, they were treated with 50 micrograms CuCl2 per 0.1 ml distilled water at 7 days of age. The optic nerves of 1-month-old hemizygote macular mice treated with copper showed hypomyelination and unmyelinated axons, while 1-month-old heterozygote macular mice had focal demyelination of axons. The number of myelinated axons in treated hemizygotes and heterozygotes was statistically significantly lower than that in the control littermates. Oligodendrocytes form myelin sheaths. Since oligodendrocytes of the hemizygote macular mice may have lower activities of cuproenzymes, such as cytochrome oxidase and superoxide dismutase, hypomyelination is assumed to be caused by the dysfunction of oligodendrocyte.
Insights
Copper treatment in macular mice, a model for Menkes disease, revealed significant hypomyelination and unmyelinated axons in treated hemizygotes. This suggests oligodendrocyte dysfunction contributes to myelin deficits in this genetic disorder.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Menkes disease is a rare genetic disorder affecting copper metabolism.
- Macular mice serve as a valuable model for studying Menkes disease due to their genetic similarities.
- Optic nerve abnormalities are a known complication in Menkes disease.
Purpose of the Study:
- To investigate the effects of copper supplementation on the optic nerve in hemizygote macular mice, a model for Menkes disease.
- To examine the myelination status and axonal integrity in the optic nerves of treated and untreated macular mice.
- To explore the potential role of oligodendrocyte dysfunction in the observed neuropathology.
Main Methods:
- Electron microscopy was used to examine the optic nerves of macular mice.
- Hemizygote macular mice were treated with copper chloride (CuCl2) at 7 days of age.
- Optic nerves were analyzed in 1-month-old treated hemizygotes, treated heterozygotes, and control littermates.
Main Results:
- Copper-treated hemizygote macular mice exhibited hypomyelination and unmyelinated axons in their optic nerves.
- Focal demyelination was observed in the optic nerves of copper-treated heterozygote macular mice.
- A statistically significant reduction in myelinated axons was noted in treated hemizygotes and heterozygotes compared to controls.
Conclusions:
- Copper treatment in hemizygote macular mice leads to significant hypomyelination and axonal damage in the optic nerve.
- Oligodendrocyte dysfunction, potentially due to reduced cuproenzyme activity, is hypothesized to cause hypomyelination in Menkes disease models.
- These findings highlight the critical role of copper in maintaining optic nerve health and myelination.