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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3352-3362. Prepublished online as a Blood First Edition Paper on January 28, 2009; DOI 10.1182/blood-2008-08-172841. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-08-172841v1 113/14/3352    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rank, G. Articles by Jane, S. M. Search for Related Content PubMed PubMed Citation Articles by Rank, G. Articles by Jane, S. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 5, 2008 Accepted January 9, 2009 Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant Gerhard Rank, Rosemary Sutton, Vikki Marshall, Rachel J. Lundie, Jacinta Caddy, Tony Romeo, Kate Fernandez, Matthew P. McCormack, Brian M. Cooke, Simon J. Foote, Brendan S. Crabb, David J. Curtis, Douglas J. Hilton, Benjamin T. Kile, and Stephen M. Jane* Rotary Bone Marrow Research Laboratory, Melbourne Health Research Directorate, Parkville, VIC, Australia The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia Electron Microscopy Unit, University of Sydney, Sydney, NSW, Australia Department of Microbiology, Monash University, Clayton, VIC, Australia Department of Medicine, University of Melbourne, Parkville, VIC, Australia * Corresponding author; email: jane{at}wehi.edu.au. Insights into the role of Ankyrin-1 (Ank-1) in the formation and stabilization of the red cell cytoskeleton have come from studies on the nb/nb mice, which carry hypomorphic alleles of Ank-1. Here, we revise several paradigms established in the nb/nb mice through analysis of an ENU-induced Ank-1-null mouse. Mice homozygous for the Ank-1 mutation are profoundly anemic in utero, and most die perinatally, indicating that Ank-1 plays a non-redundant role in erythroid development. The surviving pups exhibit features of severe hereditary spherocytosis (HS), with marked hemolysis, jaundice, compensatory extramedullary erythropoiesis, and tissue iron overload. Red cell membrane analysis reveals a complete loss of ANK-1 protein, and a marked reduction in -spectrin. As a consequence, the red cells exhibit total disruption of cytoskeletal architecture, and severely altered hemorheological properties. Heterozygous mutant mice, which have wild type levels of ANK-1 and spectrin in their RBC membranes, and normal red cell survival and ultrastructure, exhibit profound resistance to malaria, which is not due to impaired parasite entry into RBC. These findings provide novel insights into the role of Ank-1, and define an ideal model for the study of HS and malarial resistance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. A. Anong, T. Franco, H. Chu, T. L. Weis, E. E. Devlin, D. M. Bodine, X. An, N. Mohandas, and P. S. Low Adducin forms a bridge between the erythrocyte membrane and its cytoskeleton and regulates membrane cohesion Blood, August 27, 2009; 114(9): 1904 - 1912. [Abstract] [Full Text] [PDF]

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