Changes of copper level and cytochrome c oxidase activity in the macular mouse with age

Meguro, Yuko; Kodama, Hiroko; Abe, Toshiaki; Kobayashi, S.; Kodama, Yukio; Nishimura, Masahiko

doi:10.1016/s0387-7604(12)80027-1

Cited by 26 publications

(13 citation statements)

References 19 publications

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“…24,25 The defects in ATP7A that cause Menkes disease encompass a diverse range of genetic mutations, 26–30 a considerable proportion of which lead to complete loss of function of the transporter, a circumstance in which even early copper treatment bestows limited benefit. 24,31–33 Naturally occurring mouse models of Menkes disease exist 34–37 and have been studied to evaluate potential therapies for this disorder. 37–40 …”

Section: Introductionmentioning

confidence: 99%

ATP7A-related copper transport diseases—emerging concepts and future trends

2011

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This Review summarizes recent advances in understanding copper-transporting ATPase 1 (ATP7A), and examines the neurological phenotypes associated with dysfunction of this protein. Involvement of ATP7A in axonal outgrowth, synapse integrity and neuronal activation underscores the fundamental importance of copper metabolism to neurological function. Defects in ATP7A cause Menkes disease, an infantile-onset, lethal condition. Neonatal diagnosis and early treatment with copper injections enhance survival in patients with this disease, and can normalize clinical outcomes if mutant ATP7A molecules retain small amounts of residual activity. Gene replacement rescues a mouse model of Menkes disease, suggesting a potential therapeutic approach for patients with complete loss-of-function ATP7A mutations. Remarkably, a newly discovered ATP7A disorder—isolated distal motor neuropathy—has none of the characteristic clinical or biochemical abnormalities of Menkes disease or its milder allelic variant occipital horn syndrome (OHS), instead resembling Charcot–Marie–Tooth disease type 2. These findings indicate that ATP7A has a crucial but previously unappreciated role in motor neuron maintenance, and that the mechanism underlying ATP7A-related distal motor neuropathy is distinct from Menkes disease and OHS pathophysiology. Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function.

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Section: Introductionmentioning

confidence: 99%

ATP7A-related copper transport diseases—emerging concepts and future trends

2011

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“…Because macular mice possess a mutation in the mottled gene (atp7a) and have a clinical phenotype and biochemical abnormalities similar to those of MD patients, they can serve as an animal model for MD (i.e., MD model mice) (5-7). Systemic copper deficiency was demonstrated to cause dysfunction of copper-dependent enzymes and to result in multisystem disorders, such as severe neurodegeneration, connective tissue abnormalities, and kinky hair, in these mice (8,9).…”

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confidence: 99%

PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

Nomura

Nozaki²,

Hamazaki

et al. 2014

J Nucl Med

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Menkes disease (MD), an X-linked recessive disorder of copper metabolism caused by mutations in the copper-transporting ATP7A gene, results in growth failure and severe neurodegeneration in early childhood. Subcutaneous copper-histidine injection is the standard treatment for MD, but it has limited clinical efficacy. Furthermore, long-term copper injection causes excess copper accumulation in the kidneys, resulting in renal dysfunction. To attempt to resolve this issue, we used PET imaging with 64 Cu to investigate the effects of disulfiram on copper biodistribution in living mice serving as an animal model for MD (MD model mice). Methods: Macular mice were used as MD model mice, and C3H/He mice were used as wild-type mice. Mice were pretreated with 2 types of chelators (disulfiram, a lipophilic chelator, and D-penicillamine, a hydrophilic chelator) 30 min before 64 CuCl 2 injection. After 64 CuCl 2 injection, emission scans covering the whole body were performed for 4 h. After the PET scans, the brain and kidneys were analyzed for radioactivity with γ counting and autoradiography. Results: After copper injection alone, marked accumulation of radioactivity ( 64 Cu) in the liver was demonstrated in wild-type mice, whereas in MD model mice, copper was preferentially accumulated in the kidneys (25.56 ± 3.01 percentage injected dose per gram [%ID/g]) and was detected to a lesser extent in the liver (13.83 ± 0.26 %ID/g) and brain (0.96 ± 0.08 %ID/g). Copper injection with disulfiram reduced excess copper accumulation in the kidneys (14.54 ± 2.68 %ID/g) and increased copper transport into the liver (29.42 ± 0.98 %ID/g) and brain (5.12 ± 0.95 %ID/g) of MD model mice. Copper injection with D-penicillamine enhanced urinary copper excretion and reduced copper accumulation in most organs in both mouse groups. Autoradiography demonstrated that disulfiram pretreatment induced copper transport into the brain parenchyma and reduced copper accumulation in the renal medulla. Conclusion: PET studies with 64 Cu revealed that disulfiram had significant effects on the copper biodistribution of MD. Disulfiram increased copper transport into the brain and reduced copper uptake in the kidneys of MD model mice. The application of 64 Cu PET for the treatment of MD and other copperrelated disorders may be useful in clinical settings.

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“…Hemizygote macular mice lost their appetite at 10 days and died at 14 or 15 days of age. Fifty micrograms CuCl # per 0n1 ml distilled water was injected into the abdomens of 7-day-old hemizygote macular mice under diethylether anesthesia at only once (Mann et al, 1979 ;Meguro et al, 1991 ; 0014-4835\99\010059j07 $30.00\0…”

Section: Methodsmentioning

confidence: 99%

“…Copper, zinc and manganese are considered to be associated with metalloenzymes, and previous studies have shown that the activity of copper-containing enzymes such as dopamine β-hydroxylase, cytochrome oxidase, and superoxide dismutase is reduced in copper-deficient conditions (Meguro et al, 1991). Menkes' disease is due to copper deficiency and shows progressive neurodegeneration, specific hair features, low body temperature and blood vessel changes (Menkes et al, 1962 ;Bray, 1965 ;Aguilar et al, 1966 ;Danks et al, 1972).…”

Section: Introductionmentioning

confidence: 99%

X-ray Microanalysis of Melanin Granules of Retinal Pigment Epithelium and Choroid in Hereditary Copper Deficient Mice (Macular Mice)

Mishima

Amemiya

Takano

1999

Experimental Eye Research

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Changes of copper level and cytochrome c oxidase activity in the macular mouse with age

Cited by 26 publications

References 19 publications

ATP7A-related copper transport diseases—emerging concepts and future trends

ATP7A-related copper transport diseases—emerging concepts and future trends

PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

X-ray Microanalysis of Melanin Granules of Retinal Pigment Epithelium and Choroid in Hereditary Copper Deficient Mice (Macular Mice)

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Changes of copper level and cytochrome c oxidase activity in the macular mouse with age

Cited by 26 publications

References 19 publications

ATP7A-related copper transport diseases—emerging concepts and future trends

ATP7A-related copper transport diseases—emerging concepts and future trends

PET Imaging Analysis with 64Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

X-ray Microanalysis of Melanin Granules of Retinal Pigment Epithelium and Choroid in Hereditary Copper Deficient Mice (Macular Mice)

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PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model