ATP7A transgenic and nontransgenic mice are resistant to high copper exposure

Ke, Bi-Xia, Llanos, Roxana M. and Mercer, Julian F. B. 2008, ATP7A transgenic and nontransgenic mice are resistant to high copper exposure, Journal of nutrition, vol. 138, no. 4, pp. 693-697.

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Title ATP7A transgenic and nontransgenic mice are resistant to high copper exposure
Author(s) Ke, Bi-Xia
Llanos, Roxana M.
Mercer, Julian F. B.
Journal name Journal of nutrition
Volume number 138
Issue number 4
Start page 693
End page 697
Total pages 5
Publisher American Society of Nutrition
Place of publication Bethesda, Md.
Publication date 2008-04
ISSN 0022-3166
Summary The protein affected in Menkes disease, ATP7A, is a copper (Cu)-transporting P-type ATPase that plays an important role in Cu homeostasis, but the full extent of this role has not been defined at a systemic level. Transgenic mice that overexpress the human ATP7A from the chicken β-actin composite promoter (CAG) were used to further investigate the physiological function of ATP7A. Overexpression of ATP7A in the mice caused disturbances in Cu homeostasis, with depletion of Cu in some tissues, especially the heart. To investigate the effect of overexpression of ATP7A when dietary Cu intake was markedly increased, normal and transgenic mice were exposed to drinking water containing 300 mg/L of Cu as Cu acetate for 3 mo. Cu exposure resulted in partial restoration of heart Cu concentrations in male transgenic mice. Despite the extended period of Cu exposure, Cu concentrations in the liver remained relatively unaffected, with a significant increase in male nontransgenic mice. Liver pathology was unremarkable except for small areas of fibrosis that were detected only in livers of the Cu-exposed transgenic mice. Intracellular localization of ATP7A in various tissues was not affected by Cu exposure. Plasma Cu concentration and ceruloplasmin oxidase activity were reduced in both Cu-exposed transgenic and nontransgenic mice. The expression levels of other candidate Cu homeostatic proteins, endogenous Atp7b, ceruloplasmin, Ctr1, and transgenic ATP7A were not altered significantly by Cu exposure. Overall, mice are remarkably resistant to high Cu loads and the overexpression of ATP7A has only moderate effects on the response to Cu exposure. © 2008 American Society for Nutrition.
Language eng
Field of Research 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics)
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, American Society of Nutrition
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Document type: Journal Article
Collection: School of Life and Environmental Sciences
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