Imperial College London
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DrSophieRutschmann

Faculty of Medicine, Department of Immunology and Inflammation

Reader in Immunology
 
 
 
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Contact

 

s.rutschmann Website

 
 
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Location

 

9N4bHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Siggs:2012:10.1073/pnas.1211499109,
author = {Siggs, OM and Cruite, JT and Du, X and Rutschmann, S and Masliah, E and Beutler, B and Oldstone, MBA},
doi = {10.1073/pnas.1211499109},
journal = {Proc Natl Acad Sci U S A},
pages = {13733--13738},
title = {Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease.},
url = {http://dx.doi.org/10.1073/pnas.1211499109},
volume = {109},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Copper influences the pathogenesis of prion disease, but whether it is beneficial or detrimental remains controversial. Copper homeostasis is also essential for normal physiology, as highlighted by the spectrum of diseases caused by disruption of the copper transporting enzymes ATP7A and ATP7B. Here, by using a forward genetics approach in mice, we describe the isolation of three alleles of Atp7a, each with different phenotypic consequences. The mildest of the three, Atp7a(brown), was insufficient to cause lethality in hemizygotes or mottling of the coat in heterozygotes, but did lead to coat hypopigmentation and reduced copper content in the brains of hemizygous males. When challenged with Rocky Mountain Laboratory scrapie, the onset of prion disease was delayed in Atp7a(brown) mice, and significantly less proteinase-resistant prion protein was found in the brains of moribund Atp7a(brown) mice compared with WT littermates. Our results establish that ATP7A-mediated copper homeostasis is important for the formation of pathogenic proteinase-resistant prion protein.
AU  - Siggs,OM
AU  - Cruite,JT
AU  - Du,X
AU  - Rutschmann,S
AU  - Masliah,E
AU  - Beutler,B
AU  - Oldstone,MBA
DO  - 10.1073/pnas.1211499109
EP  - 13738
PY  - 2012///
SP  - 13733
TI  - Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease.
T2  - Proc Natl Acad Sci U S A
UR  - http://dx.doi.org/10.1073/pnas.1211499109
UR  - https://www.ncbi.nlm.nih.gov/pubmed/22869751
VL  - 109
ER  -
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