Heterozygous tx mice have an increased sensitivity to copper loading: implications for Wilson's Disease carriers

Cheah, Daphne M. Y., Deal, Yolanda J., Wright, Paul F. A., Buck, Nicole E., Chow, Chung Wo, Mercer, Julian and Allen, Katrina J. 2007, Heterozygous tx mice have an increased sensitivity to copper loading: implications for Wilson's Disease carriers, BioMetals, vol. 20, no. 5, pp. 751-757, doi: 10.1007/s10534-006-9038-7.

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Title Heterozygous tx mice have an increased sensitivity to copper loading: implications for Wilson's Disease carriers
Author(s) Cheah, Daphne M. Y.
Deal, Yolanda J.
Wright, Paul F. A.
Buck, Nicole E.
Chow, Chung Wo
Mercer, Julian
Allen, Katrina J.
Journal name BioMetals
Volume number 20
Issue number 5
Start page 751
End page 757
Publisher Springer Netherlands
Place of publication Amsterdam, The Netherlands
Publication date 2007-10
ISSN 0966-0844
Keyword(s) chronic copper exposure
Wilson's disease
Wilson's disease carriers
tx mouse
Summary Wilson's disease carriers constitute 1% of the human population. It is unknown whether Wilsons disease carriers are at increased susceptibility to copper overload when exposed to chronically high levels of ingested copper. This study investigated the effect of chronic excess copper in drinking water on the heterozygous form of the Wilson’s disease mouse model – the toxic milk (tx) mouse. Mice were provided with drinking water containing 300 mg/l copper for 4–7, 8–11, 12–15 or 16–20 months. At the completion of the study liver, spleen, kidney and brain tissue were analyzed by atomic absorption spectroscopy to determine copper concentration. Plasma ceruloplasmin oxidase activity and liver histology were also assessed. Chronic copper loading resulted in significantly increased liver copper in both tx heterozygous and tx homozygous mice, while wild type mice were resistant to the effects of copper loading. Copper loading effects were greatest in tx homozygous mice, with increased extrahepatic copper deposition in spleen and kidney – an effect absent in heterozygote and wild type mice. Although liver histology in homozygous mice was markedly abnormal, no histological differences were noted between heterozygous and wild type mice with copper loading. Tx heterozygous mice have a reduced ability to excrete excess copper, indicating that half of the normal liver Atp7b copper transporter activity is insufficient to deal with large copper intakes. Our results suggest that Wilsons disease carriers in the human population may be at increased risk of copper loading if chronically exposed to elevated copper in food or drinking water.
Language eng
DOI 10.1007/s10534-006-9038-7
Field of Research 110307 Gastroenterology and Hepatology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2006, Springer
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007650

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