Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies by others indicated that alterations in brain catecholamines were different for perinatal copper deficiency produced by diet in rats and that resulting from a genetic mutation of the X-chromosome, Menkes' syndrome in humans and brindled mice. Thus, copper deficiency was studied in a model in which dietary and genetic deficiency (brindled mice) were compared in two strains of the same species. C57BL and C3H/HeJ mice. Dietary copper deficiency was also produced in rats for comparison. In brain, both dietary and genetic copper deficiency resulted in impaired growth, low brain copper levels, greatly decreased norepinephrine concentrations but normal dopamine levels. The activity of brain cytochrome oxidase was greatly depressed following both dietary and genetic copper deficiency, suggesting a functional deficit of copper. However, the activity of another cuproenzyme, dopamine-beta-hydroxylase, was significantly elevated in deficient animals. The elevation was observed when either copper or N-ethylmaleimide was added to inactivate an endogenous inhibitor. The cause of low brain norepinephrine remains unknown; however, depressed brain norepinephrine may be partly responsible for functional changes in the deficient animals, such as hypomyelination, since the activity of the myelin protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, was lower in the most deficient animals.
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PMID:Effect of dietary or genetic copper deficiency on brain catecholamines, trace metals and enzymes in mice and rats. 628 8

Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A). In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene) is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes). This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.
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PMID:Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain. 2693 6