{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:37:59Z","timestamp":1791128279947,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,8,21]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>Atp7a<\/jats:italic>\n                    , each with different phenotypic consequences. The mildest of the three,\n                    <jats:italic>\n                      Atp7a\n                      <jats:sup>brown<\/jats:sup>\n                    <\/jats:italic>\n                    , 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\n                    <jats:italic>\n                      Atp7a\n                      <jats:sup>brown<\/jats:sup>\n                    <\/jats:italic>\n                    mice, and significantly less proteinase-resistant prion protein was found in the brains of moribund\n                    <jats:italic>\n                      Atp7a\n                      <jats:sup>brown<\/jats:sup>\n                    <\/jats:italic>\n                    mice compared with WT littermates. Our results establish that ATP7A-mediated copper homeostasis is important for the formation of pathogenic proteinase-resistant prion protein.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1211499109","type":"journal-article","created":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T22:50:06Z","timestamp":1344293406000},"page":"13733-13738","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Disruption of copper homeostasis due to a mutation of\n                    <i>Atp7a<\/i>\n                    delays the onset of prion disease"],"prefix":"10.1073","volume":"109","author":[{"given":"Owen M.","family":"Siggs","sequence":"first","affiliation":[{"name":"Departments of aGenetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin T.","family":"Cruite","sequence":"additional","affiliation":[{"name":"Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[{"name":"Departments of aGenetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Rutschmann","sequence":"additional","affiliation":[{"name":"Departments of aGenetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliezer","family":"Masliah","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Beutler","sequence":"additional","affiliation":[{"name":"Departments of aGenetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B. A.","family":"Oldstone","sequence":"additional","affiliation":[{"name":"Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/37783"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci700226c"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00160.2005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00196.2003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001472t"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1233"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2384"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000390"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.25.19121"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403467200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2004.090"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009666200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.05.013"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03650.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.40.25545"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3440001"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300303200"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.07.051"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2003.09.014"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.1932.tb03587.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.1937.tb04108.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.50.2.188"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1354"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.180"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-7"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-20"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-14"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094-195"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.027"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1293-327"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1293-344"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.052746"},{"key":"e_1_3_3_33_2","unstructured":"OM Siggs NG Smart AR Murray B Beutler Record for brown. 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