{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:02:22Z","timestamp":1784224942738,"version":"3.55.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,6,22]]},"abstract":"<jats:p>\n                    A somatic mutation in the X linked\n                    <jats:italic>PIGA<\/jats:italic>\n                    gene is responsible for the deficiency of glycosyl phosphatidylinositol (GPI)-anchored proteins on blood cells from patients with paroxysmal nocturnal hemoglobinuria. No inherited form of GPI-anchor deficiency has been described. Because conventional\n                    <jats:italic>Piga<\/jats:italic>\n                    gene knockout is associated with high embryonic lethality in chimeric mice, we used the Cre\/loxP system. We generated mice in which two loxP sites flank part of\n                    <jats:italic>Piga<\/jats:italic>\n                    exon 2. After crossbreeding with female mice of the\n                    <jats:italic>EIIa-cre<\/jats:italic>\n                    strain, the floxed allele undergoes Cre-mediated recombination with high efficiency during early embryonic development. Because of X chromosome inactivation, female offspring are mosaic for cells that express or lack GPI-linked proteins. Analysis of mosaic mice showed that in heart, lung, kidney, brain, and liver, mainly wild-type\n                    <jats:italic>Piga<\/jats:italic>\n                    is active, suggesting that these tissues require GPI-linked proteins. The salient exceptions were spleen, thymus, and red blood cells, which had almost equal numbers of cells expressing the wild-type or the recombined allele, implying that GPI-linked proteins are not essential for the derivation of these tissues. PIGA(\u2212) cells had no growth advantage, suggesting that other factors are needed for their clonal dominance in patients with paroxysmal nocturnal hemoglobinuria.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.13.7479","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"7479-7483","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["X inactivation and somatic cell selection rescue female mice carrying a\n                    <i>Piga<\/i>\n                    -null mutation"],"prefix":"10.1073","volume":"96","author":[{"given":"Peter","family":"Keller","sequence":"first","affiliation":[{"name":"Division of Hematology, Departments of Internal Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabi","family":"Tremml","sequence":"additional","affiliation":[{"name":"Division of Hematology, Departments of Internal Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Rosti","sequence":"additional","affiliation":[{"name":"Division of Hematology, Departments of Internal Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Bessler","sequence":"additional","affiliation":[{"name":"Division of Hematology, Departments of Internal Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,6,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7680492"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.4.877"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06240.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90250-T"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.5.751"},{"key":"e_1_3_3_6_2","first-page":"149","volume":"35","author":"Bessler M","year":"1998","unstructured":"M Bessler, P Hillmen Semin Hematol 35, 149\u2013167 (1998).","journal-title":"Semin Hematol"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0200243"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/978-3-642-88178-7","volume-title":"Chromosomes and Sex-linked Genes","author":"Ohno S","year":"1967","unstructured":"S Ohno Chromosomes and Sex-linked Genes, ed S Ohno (Springer, Berlin), pp. 46\u201369 (1967)."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.9.3600.bloodjournal8793600"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119613"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.14.5166"},{"key":"e_1_3_3_12_2","unstructured":"Tremml G. 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