title: Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anaemia despite a normal membrane skeleton.
abstract: Band 3 is the most abundant integral protein of the red blood cell membrane. It performs two critical biological functions: maintaining ionic homeostasis, by transporting Cl- and HCO3-ions, and providing mechanical stability to the erythroid membrane. Erythroid band 3 (AE1) is one of three anion exchangers that are encoded by separate genes. The AE1 gene is transcribed by two promoters: the upstream promoter produces erythroid band 3, whereas the downstream promoter initiates transcription of the band 3 isoform in kidney. To assess the biological consequences of band 3 deficiency, we have selectively inactivated erythroid but not kidney band 3 by gene targeting in mice. Although no death in utero occurred, the majority of homozygous mice die within two weeks after birth. The erythroid band 3 null mice show retarded growth, spherocytic red blood cell morphology and severe haemolytic anaemia. Remarkably, the band 3-/- red blood cells assembled normal membrane skeleton thus challenging the notion that the presence of band 3 is required for the stable biogenesis of membrane skeleton. The availability of band 3-/- mice offers a unique opportunity to investigate the role of erythroid band 3 in the regulation of membrane-skeletal interactions, anion transport and the invasion and growth of malaria parasite into red blood cells.
authors.affiliation: Department of Biomedical Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Southgate
authors.forename: A H
authors.initials: AH
authors.lastname: Chishti
authors.forename: B
authors.initials: B
authors.lastname: Mitchell
authors.forename: S J
authors.initials: SJ
authors.lastname: Yi
authors.forename: J
authors.initials: J
authors.lastname: Palek
mesh_terms: D000483:Alleles; D000743:Anemia, Hemolytic / Q000097:blood* / Q000235:genetics; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000648:ultrastructure; D004910:Erythrocyte Membrane / Q000737:chemistry; D004912:Erythrocytes / Q000737:chemistry / Q000648:ultrastructure; D018390:Gene Targeting; D005796:Genes / Q000235:genetics; D006128:Growth; D006720:Homozygote; D007668:Kidney / Q000737:chemistry / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008817:Mice, Mutant Strains; D013102:Spherocytes / Q000166:cytology* / Q000648:ultrastructure; D013163:Splenomegaly
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D008565:Membrane Proteins