Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency.
Anemia-Dyserythropoietic-Congenital, Animal, Animals-Genetically-Modified, Anion-Exchange-Protein-1-Erythrocyte, Erythropoiesis, Gene-Expression-Regulation-Developmental, Human, In-Situ-Hybridization-Fluorescence, Mice, Mice-Inbred-C57BL, Mice-Knockout, Mitosis, Molecular-Sequence-Data, Mutation, Phenotype, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Zebrafish
Nat Genet 2003 May; 34(1):59-64.
Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage. Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis.
Paw, B H.; Davidson, A J.; Zhou, Y; Li, R; Lee, C; Donovan, A; Drejer, A H.; Gwynn, B; Peters, L L.; Chernova, M N.; Wickramasinghe, S N.; Lee, M J.; Lux, S E.; and et, al, " Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency." (2003). Faculty Research 2000 - 2009. 538.