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dc.contributor.authorWang, Yanfang  Concept link
dc.contributor.authorZhu, Sha  Concept link
dc.contributor.authorWeisman, Gary A.  Concept link
dc.contributor.authorGitlin, Jonathan D.  Concept link
dc.contributor.authorPetris, Michael J.  Concept link
dc.identifier.citationPLoS ONE 7 (2012): e43039en_US
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.abstractThe 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.sponsorshipThis 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.publisherPublic Library of Scienceen_US
dc.rightsAttribution 3.0 United States*
dc.titleConditional knockout of the Menkes disease copper transporter demonstrates its critical role in embryogenesisen_US

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Attribution 3.0 United States
Except where otherwise noted, this item's license is described as Attribution 3.0 United States