cDNA cloning and genomic organization of the murine MRP7, a new ATP-binding cassette transporter

Cellular resistance to cytotoxic drugs is a major obstacle to the treatment of disseminated cancers. Multidrug resistance protein (MRP) subfamily is a member of the ATP-binding cassette transporters which has been shown to cause multidrug resistance, except for P-glycoprotein. A new MRP subfamily gene, mrp7A (Abcc10), and its splicing variant, mrp7B, were isolated from mouse. The lengths of the open reading frames of mouse mrp7A and mrp7B are 4383 and 4506 bp, respectively. Estimated polypeptide sequences of mrp7A and mrp7B are 1460 and 1501 amino acids. The mouse mrp7 gene consists of at least 21 exons and 20 introns spanning around 20 kb that is almost the same as the one in human MRP7 gene, but different with the other MRP subfamily genes. The promoter region was isolated from the genomic clone and shown to support the luciferase activity seven fold over the promoterless negative control and two fold activity higher than the positive control of SV40 promoter. The analysis of tissue expression of mrp7A and mrp7B showed that these two transcripts express differentially in specific tissues.