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Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant

Citation

Rank, G and Sutton, R and Marshall, V and Lundie, RJ and Caddy, J and Romeo, T and Fernandez, K and McCormack, MP and Cooke, BM and Foote, SJ and Crabb, BS and Curtis, DJ and Hilton, DJ and Kile, BT and Jane, SM, Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant, Blood, 113, (14) pp. 3352-3362. ISSN 0006-4971 (2009) [Refereed Article]

DOI: doi:10.1182/blood-2008-08-172841

Abstract

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 N-ethyl-N-nitrosourea (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 nonredundant 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 B- spectrin. As a consequence, the red cells exhibit total disruption of cytoskeletal architecture and severely altered hemorheologic 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Haematology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Blood Disorders
Author:Foote, SJ (Professor Simon Foote)
ID Code:60301
Year Published:2009
Web of Science® Times Cited:32
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-01-28
Last Modified:2010-04-15
Downloads:0

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