Abstract
Band 3 is the most abundant integral protein of the red blood cell membrane1,2. It performs two critical biological functions: maintaining ionic homeostasis, by transporting Cl– and HCO3– ions, and providing mechanical stability to the erythroid membrane1,2. Erythroid band 3 (AE1) is one of three anion exchangers that are encoded by separate genes3. 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 kidney4. 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.
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Southgate, C., Chishti, A., Mitchell, B. et al. Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anaemia despite a normal membrane skeleton. Nat Genet 14, 227–230 (1996). https://doi.org/10.1038/ng1096-227
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DOI: https://doi.org/10.1038/ng1096-227
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