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Biochemical and Biophysical Research... Jul 2019ABCD4, a member of the ATP-binding cassette transporter superfamily, is associated with the transport of vitamin B which is crucial for the development of red blood...
ABCD4, a member of the ATP-binding cassette transporter superfamily, is associated with the transport of vitamin B which is crucial for the development of red blood cells (RBCs) and may also be involved in its metabolism. However, the molecular function of ABCD4 during RBC development in zebrafish is mostly unknown. Using a morpholino-based knockdown approach, we found that abcd4-knockdown resulted in abnormal RBCs of irregular shapes and various sizes. o-Dianisidine staining, as an indicator of hemoglobin in RBCs, further confirmed that abcd4 morphants possessed fewer hemoglobinized cells and impaired blood circulation. Multiple protein sequence alignment revealed that the amino acid sequence for residues 13-292, which is the domain of vitamin B transport, of the zebrafish Abcd4 was highly conserved compared to that of other species. Accordingly, the abcd4 morphants can be rescued with human ABCD4, demonstrating a conserved role of ABCD4 in vertebrates. Notably, the vitamin B-deficient phenotype in abcd4 morphants, which causes anemia, was recapitulated in the newly-established abcd4 mutant, indicating the possibility that the abcd4 mutant could be used as a disease model of vitamin B-deficiency anemia. Our study provides an insight that the analysis of the newly-established abcd4 mutant may contribute to understanding its roles in ABCD4-related vitamin B-deficiency anemia and the associated pathogeneses in humans.
Topics: ATP-Binding Cassette Transporters; Anemia; Animals; Mutation; Vitamin B 12 Deficiency; Zebrafish
PubMed: 31113616
DOI: 10.1016/j.bbrc.2019.05.099