Conditional knockout of the Menkes disease copper transporter demonstrates its critical role in embryogenesis


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dc.contributor.author Wang, Yanfang
dc.contributor.author Zhu, Sha
dc.contributor.author Weisman, Gary A.
dc.contributor.author Gitlin, Jonathan D.
dc.contributor.author Petris, Michael J.
dc.date.accessioned 2012-09-28T20:27:07Z
dc.date.available 2012-09-28T20:27:07Z
dc.date.issued 2012-08-10
dc.identifier.citation PLoS ONE 7 (2012): e43039 en_US
dc.identifier.uri http://hdl.handle.net/1912/5404
dc.description © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 7 (2012): e43039, doi:10.1371/journal.pone.0043039. en_US
dc.description.abstract The transition metal, copper (Cu), is an enzymatic cofactor required for a wide range of biochemical processes. Its essentiality is demonstrated by Menkes disease, an X-linked copper deficiency disorder characterized by defects in nervous-, cardiovascular- and skeletal systems, and is caused by mutations in the ATP7A copper transporter. Certain ATP7A mutations also cause X-linked Spinal Muscular Atrophy type 3 (SMAX3), which is characterized by neuromuscular defects absent an underlying systemic copper deficiency. While an understanding of these ATP7A-related disorders would clearly benefit from an animal model that permits tissue-specific deletion of the ATP7A gene, no such model currently exists. In this study, we generated a floxed mouse model allowing the conditional deletion of the Atp7a gene using Cre recombinase. Global deletion of Atp7a resulted in morphological and vascular defects in hemizygous male embryos and death in utero. Heterozygous deletion in females resulted in a 50% reduction in live births and a high postnatal lethality. These studies demonstrate the essential role of the Atp7a gene in mouse embryonic development and establish a powerful model for understanding the tissue-specific roles of ATP7A in copper metabolism and disease. en_US
dc.description.sponsorship This work was supported by National Institutes of Health Grants DK59893 and DK093386 to M.J.P., and DK44464 to J.D.G. en_US
dc.format.mimetype application/pdf
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.uri http://dx.doi.org/10.1371/journal.pone.0043039
dc.rights.uri http://creativecommons.org/licenses/by/3.0/us/ *
dc.title Conditional knockout of the Menkes disease copper transporter demonstrates its critical role in embryogenesis en_US
dc.type Article en_US
dc.identifier.doi 10.1371/journal.pone.0043039

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