ABC TRANSPORTERS IN HUMAN DISEASE AND DRUG RESISTANCE

三磷酸腺苷结合盒(ABC)基因家族编码一组不同的 转运蛋白将各种各样的化合物输送到 细胞和组织的膜。人类的ABC基因涉及到许多 疾病，包括囊性纤维化、肾上腺皮质营养不良，以及 家族性持续性高胰岛素血症。肿瘤的抗药性 对多种药物(多药耐药，MDR)的主要限制 癌症化疗。在某些肿瘤中，MDR与 P-糖蛋白/(Pgp)多药耐药与多药耐药 相关蛋白(MRP)基因。PGP和MRP是ABC家族的转运蛋白。 我们之前已经发现了21个新的人类ABC基因。基因 这些基因的位置以及它们的表达模式 已经确定了。其中一种基因，abcr，只在 视网膜。该基因被定位在染色体1p13-21上。 一种隐性遗传病--Stargardt黄斑营养不良(STGD1)基因 导致儿童视力丧失。我们总共确定了19种不同的 STGD1患者ABCR基因的突变，包括几个框架- 移位和无意义等位基因。STGD1的表型与年龄相似- 相关性黄斑变性(AMD)，视网膜的一种常见形式 发生在65岁以上的人身上的退行性疾病。我们检查了一组 167名AMD患者，发现其中16%的人ABCR基因突变 吉恩。了解该基因突变在STGD1和AMD中的作用， 而识别ABCR的正常功能将有助于揭示 黄斑变性的发展。对其他的进一步描述 ABC基因可能提供有关其他人类疾病和肿瘤的信息。

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. Human ABC genes are involved in a number of diseases, including cystic fibrosis, adrenoleuko-dystrophy, and familial persistent hyperinsulinemic hypoglycemia. Resistance of tumors to multiple drugs (multidrug resistance, MDR) is a major limitation of cancer chemotherapy. MDR is associated in certain tumors with the overexpression of the P-glycoprotein/(PGP)MDR and multidrug resistance- related protein (MRP) genes. PGP and MRP are ABC family transporters. We have previously identified over 21 new human ABC genes. The genetic location of each of these genes as well as their expression pattern has been determined. One of these genes, ABCR, is expressed exclusively in the retina. The gene was mapped to chromosome 1p13- 21, the location of the Stargardt macular dystrophy (STGD1) gene, a recessive disorder causing vision loss in children. We identified a total of 19 different mutations in the ABCR gene in STGD1 patients, including several frame- shift and non-sense alleles. STGD1 is phenotypically similar to age- related macular degeneration (AMD), a common form of retinal degeneration that occurs in people over age 65. We examined a cohort of 167 AMD patients and found that 16% of them had mutations in the ABCR gene. Understanding the role of mutations in this gene in STGD1 and AMD, and identifying the normal function of ABCR should shed light on the development of macular degeneration. Further characterization of other ABC genes may provide information on other human diseases and neoplasms.