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, Stephen M Jane
BLOOD | AMER SOC HEMATOLOGY | Published : 2009
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..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by National Institutes of Health
Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
The authors thank Xiuli An and Connie Birkenmeier for the kind gift of reagents; Alana Auden, Sarah King, Loretta Cerruti, and Jason Corbin for excellent technical assistance; and Lan Ta and WEHI Bioservices staff for outstanding animal husbandry.This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC; no. 382900); fellowships from the NHMRC to D.J.H., S.M.J.; a fellowship of the Australian Research Council to B. T. K.; and a Program Grant from the National Institutes of Health (Bethesda, MD; PO1 HL53749-03).