ABC Transporters in Human Disease & Multidrug Resistance

atp结合盒（ABC）基因家族编码一组不同的转运蛋白，这些转运蛋白将各种各样的化合物输送到细胞和组织的膜上。几种人类ABC转运蛋白在耐化疗药物的肿瘤细胞中过度表达。此外，一些ABC基因（CFTR, ABCC8, ABCD1）在遗传性疾病中发生突变。人类有48个ABC基因，分为7个亚家族。最近报道的ABCA12在胃和皮肤中表达，而ABCA13在气管、睾丸和骨髓中表达。小鼠基因组中存在一组abca3样基因，这些基因仅在睾丸中表达，可能与精子成熟有关。我们已经证实，由于肺表面活性物质分泌导致新生儿呼吸衰竭的患儿中ABCA3基因发生突变。ABCA3基因在肺泡II型细胞中表达，在肺泡II型细胞中产生表面活性剂。这些患者肺组织的超微分析显示肺泡细胞中有异常的板层体。该基因的进一步表征将有助于了解表面活性剂分泌和肺功能。在斑马鱼中对ABC基因进行了注释，为研究该基因的表达和功能提供了良好的模型。

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.