Recent studies on Menkes disease are reviewed, focusing especially on copper transport in the cells. A large amount of copper accumulated in the organelle-free cytoplasm, whereas mitochondria were in a state of copper deficiency, indicating that Menkes mutation probably affects copper transport from the cytosol to the organelles in the cells. Microscopic observation of the brain of the macular mouse showed that copper accumulates in the blood vessels. Observation of the brain tissue of the macular mouse after intraventricular administration of copper revealed that copper accumulates in the glia as well as the blood vessels. Copper accumulation was also observed in cultured astrocytes, a type of glial cell, indicating that the affected astrocytes accumulate blood-borne copper and release little of it in the patients with Menkes disease. Thus the effective treatment of Menkes disease could possibly be to release trapped copper from the blood vessels and glia into the neurons.
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Editors' note. Since the submission of this paper a candidate gene for Menkes disease has been identified by three independent groups (Chelly et al 1993; Mercer et al 1993; Vulpe et al 1993). The gene product established from the nucleotide sequence is highly homologous with the P-type cation-transporting ATPases and in particular with a bacterial copper-transporting ATPase. Some patients with Menkes disease have been shown to have partial gene deletions and in others the expression of the gene transcript has been altered or reduced.
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Kodama, H. Recent developments in Menkes disease. J Inherit Metab Dis 16, 791–799 (1993). https://doi.org/10.1007/BF00711911
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