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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Changes of copper level and cytochrome c oxidase activity in the macular mouse with age. 165 7

Occipital horn syndrome (OHS; Ehlers-Danlos syndrome type IX) belongs to the category of the copper metabolism disorders and is at present being investigated biochemically as is Menkes disease. We report a case of OHS in a 34-year-old male, which we believe to be the first Japanese case. He had been noted to have psychomotor retardation since his early childhood and now presents severe psychomotor retardation and muscle atrophy. He shows characteristic facial appearance, hyperelasticity of the skin, joint subluxation and generalized muscular atrophy. Laboratory investigations revealed a low serum copper and ceruloplasmin level as well as intestinal non-absorption of copper. Radiologic imagings showed occipital exostoses and bladder diverticula. The activity of lysyl oxidase, a copper-dependent enzyme involved in cross-link formation in collagen, was decreased in a skin-biopsied specimen. Electronmicroscopic investigation of a muscle biopsy showed irregularity of the myofibrillar network and accumulation of the concentric laminated bodies in the subsarcolemmal regions.
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PMID:[Occipital horn syndrome (Ehlers-Danlos syndrome type IX) with severe psychomotor retardation and muscle atrophy--a first Japanese case]. 168 78

The distribution of immunoreactive catecholamine neurons and fibers was investigated in brindled mottled mouse, a murine model of Kinky hair syndrome (KHS), using antisera against tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH). In all mice, including normal littermate controls, a transient increase of TH-immunoreactive neurons (TH-IN) was observed in the cerebral cortex during the second postnatal week. The numbers of TH-IN were more pronounced in hemizygous brindled males (MObr/y). In addition, TH-IN appeared and rapidly increased in number in the striatum of MObr/y after postnatal day 11 (P11). Striatal TH-IN were rarely detected in controls. After cupric chloride (CuCl2) treatment, TH-IN in the striatum of some of the MObr/y mice became less conspicuous. In the substantia nigra and ventral tegmental area where TH-IN are normally present, no differences either in the immunostaining of TH-IN or the pattern of TH immunoreactive fibers were detected between MObr/y and controls. In MObr/y, a superficial plexus of DBH immunoreactive fibers was more pronounced than in controls but there were no DBH immunoreactive neurons in the cerebral cortex or striatum in any of the mice examined. Neurochemical analysis revealed a marked decrease in norepinephrine levels and increase of serotonin and its metabolites in the brain in MObr/y. Together, these data suggest that the unusual expression of TH-IN in MObr/y represents perturbations of normal development of catecholamine neurons in this copper deficient mutant mouse.
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PMID:Neurochemical and immunocytochemical studies of catecholamine system in the brindled mouse. 168 2

The brindled mottled mutant mouse, a model of Menkes' disease, has alterations in copper homeostasis which cause, among other sequelae, neuronal degeneration in selected areas of brain. This work examined the neurochemical changes at postnatal days (PND) 15, 30 and 60 in females heterozygous for the sex-linked brindled mutation. These data were compared to behavioral alterations and to fur coat color at these same time points. The brindled heterozygotic females had lower concentrations of norepinephrine (NE) in the cingulate cortex, and higher levels of dopamine or dopamine metabolites in the cingulate cortex, thalamus and hypothalamus across all ages, although the difference was greatest at PND 15. The brindled females were much less active than their normal littermates at PND 15, but the differences were no longer evident at PND 30 and 60. Mottling of the fur is believed to result from low tyrosinase activity caused by abnormalities in copper metabolism. The fur pattern and behavior of the brindled mice were highly correlated with NE levels in the cingulate cortex and thalamus. These data show that female brindled mice have neurochemical abnormalities similar to (if less severe than) the male hemizygotes, that these abnormalities are regionally specific, are most apparent prior to 30 days of age, and are linked to behavioral deficits. These data also show that the extent of such deficits can be predicted by a quantitative analysis of the fur pattern of these females.
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PMID:The female brindled mouse as a model of Menkes' disease: the relationship of fur pattern to behavioral and neurochemical abnormalities. 175 14

The copper concentration was investigated in the cultured astrocytes from macular mice, an animal model of Menkes disease. An excessive amount of copper was accumulated in the astrocytes as copper-metallothionein. These results show that the underlying genetic defect of the macular mouse is expressed in the astrocytes. A similar situation may exist in Menkes disease and cause a failure of copper transport to neurones.
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PMID:Genetic expression of Menkes disease in cultured astrocytes of the macular mouse. 177 48

In order to make clear the degree of brainstem affection in Menkes disease, it is important to investigate morphological and enzymatic changes of monoamine oxidase (MAO)-containing neurons in the brain in this disease. For this purpose, MAO activity levels in brain tissue from normal and brindled mice were examined histochemically and biochemically. A coupled peroxidatic oxidation method for the histochemistry and a rapid microfluorimetric method for the biochemical assay were adopted. Animals aged 3 days, 8 days, 13 days, 3 months and 12 months were used for the histochemical study. Three-, 7-, and 12-day-old mice were used for the biochemical study. Histochemical examinations showed no significant differences in the stainability, morphology and distribution of MAO positive neurons in the brain between normal and brindled mice at the same age. Biochemical assays revealed that MAO activity levels in the brain of the postnatal brindled mice rose with age as highly as those in the normal control mice. There were no significant differences in them between normal and brindled mice at the same age. The results indicate that in Menkes disease in mice the brainstem affection, if there is, is not so severe as to influence the morphology and enzyme activity of MAO-containing neurons.
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PMID:[Histochemical and biochemical investigations of monoamine oxidase activity level in the brain of the brindled mouse]. 179 97

The macular mouse is an X-linked recessive inherited mutant and is considered to be a model for human congenital copper deficiency, Menkes' kinky hair disease. The activity of urate oxidase, which has been believed to be a copper enzyme, and copper content in the liver of the mutant mouse were determined. The oxidase activity was maintained at normal level even though there was very low level of copper present in the liver through days 7 to 14. Copper administration increased the copper content in the liver to the normal level, but did not affect the oxidase activity.
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PMID:Urate oxidase activity and copper content in the liver of macular mutant mouse, a model animal for human congenital copper deficiency, Menkes' kinky hair disease. 181 48

These studies were designed to determine if macular mutant mouse, which is a proposed animal model of Menkes' kinky-hair disease, is sensitive to the acute toxic effect of Cu as compared to normal and heterozygote mice. Single sc injection of Cu were administered to 6- to 8-day-old mice, and mortalities were recorded for 30 days. The copper treatment at high doses (12 to 25 mg Cu/kg) was very toxic to mutant mice as compared to normal mice, and almost all mutant mice died within 10 days after injection. The effect of Cu toxicity on heterozygote mice was intermediate. The LD50 values 3 days after injection of Cu were 29.5 mg Cu/kg for normal mice, 23.5 mg Cu/kg for heterozygote mice, and 15.5 mg Cu/kg for mutant mice. In Cu-injected mutant mice (11 and 18 mg Cu/kg), significant elevations in serum aspartate aminotransferase and lactate dehydrogenase activity occurred as compared to Cu-injected normal and heterozygote mice. However, no significant elevations in serum creatinine and urea nitrogen contents in Cu-injected mutant were observed as compared to normal and heterozygote mouse. No significant differences in hepatic metallothionein(MT) and MT-1 mRNA, and serum ceruloplasmin oxidase activity levels were observed between Cu-injected normal and mutant mouse. These results indicated that macular mutant mice was sensitive to the acute toxic or hepatotoxic effects of Cu as compared to normal and heterozygote mice.
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PMID:Copper-induced toxicity in macular mutant mouse: an animal model for Menkes' kinky-hair disease. 187 75

Increasing loss of vision caused by peculiar macroscopic and functional retinal changes was the first ophthalmologic manifestation of Wilson's disease in a 22-year-old patient. Neither retinal changes nor great visual impairment has been described thus far in the literature concerning this disease. Likely correlations are discussed with Menkes syndrome, an X-linked inborn error of copper metabolism with onset in early childhood.
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PMID:[Retinal changes in Wilson's disease]. 188 68

The amount of lysine in collagen is only 3 or 4% of total aminoacids, but it has an important function in the constitution of the cross-links between the molecules to built the fibrils and the fibers of collagen. For this function, some lysine molecules must be hydroxylated and other oxidized to aldehyde compounds. Some deficits in these metabolic pathways are responsible for heritable diseases of the connectivite tissue as types IV and IX of the Ehlers-Danlos syndrome, lathyrism, the Menkes kinky hair syndrome, Cutis-Laxa or the type II of osteogenesis imperfecta. The contribution to fibrosis is also discussed.
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PMID:[Lysine and collagen]. 190 95


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