ABC Transporters in Human Disease & Multidrug Resistance

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The ATP-binding cassette (ABC) gene family encodes a diverse group of transporter proteins that pump a wide variety of compounds across the membranes of cells and tissues. Several human ABC transporters are overexpressed in tumor cells that are resistant to chemotherapy drugs. In addition, several ABC genes (CFTR, ABCC8, ABCD1) are mutated in inherited diseases. There are 48 human ABC genes, divided into 7 subfamilies. The recently described ABCA12 is expressed in the stomach and skin, and ABCA13 is expressed in the trachea, testes, and bone marrow. A cluster of ABCA3-like genes is present in the mouse genome and these genes are exclusively expressed in the testes where they may be involved in sperm maturation. We have documented that the ABCA3 gene is mutated in children with neonatal respiratory failure due to lung surfactant secretion. The ABCA3 gene is expressed in alveolal type II cells, where surfactants are produced. Ultramicroscopic analysis of lung tissue from these patients shows abnormal lamellar bodies in the alveolar cells. Further characterization of this gene should yield insights into surfactant secretion and lung function. The ABC genes were annotated in zebrafish which should be an excellent model for studying gene expression and function.