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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Holt, D. S. Articles by Morgan, B. P. Search for Related Content PubMed PubMed Citation Articles by Holt, D. S. Articles by Morgan, B. P. Related Collections Immunobiology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2001, Vol. 98, No. 2, pp. 442-449 RED CELLS Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria Dewi S. Holt, Marina Botto, Anne E. Bygrave, S. Melanie Hanna, Mark J. Walport, and B. Paul Morgan From the Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom; and the Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, London, United Kingdom. The glycolipid-anchored glycoprotein CD59 inhibits assembly of the lytic membrane attack complex of complement by incorporation into the forming complex. Absence of CD59 and other glycolipid-anchored molecules on circulating cells in the human hemolytic disorder paroxysmal nocturnal hemoglobinuria is associated with intravascular hemolysis and thrombosis. To examine the role of CD59 in protecting host tissues in health and disease, CD59-deficient (CD59/) mice were produced by gene targeting in embryonic stem cells. Absence of CD59 was confirmed by staining cells and tissues with specific antibody. Despite the complete absence of CD59, mice were healthy and fertile. Erythrocytes in vitro displayed increased susceptibility to complement and were positive in an acidified serum lysis test. Despite this, CD59/ mice were not anemic but had elevated reticulocyte counts, indicating accelerated erythrocyte turnover. Fresh plasma and urine from CD59/ mice contained increased amounts of hemoglobin when compared with littermate controls, providing further evidence for spontaneous intravascular hemolysis. Intravascular hemolysis was increased following administration of cobra venom factor to trigger complement activation. CD59/ mice will provide a tool for characterizing the importance of CD59 in protection of self tissues from membrane attack complex damage in health and during diseases in which complement is activated. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Wu, W. Hu, A. Shahsafaei, W. Song, M. Dobarro, G. K. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020