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. The human ABC transporters MDR and MRP are overexpressed in a wide variety of tumor cells that are resistant to chemotherapy drugs. In addition, several ABC genes (CFTR, SUR, ALDP) are mutated in inherited diseases. In collaboration with DCS scientists we have shown that the MXR/ABCP gene is overexpressed in several human tumor cell lines that are resistant to mitoxantrone, topotecan and several other drugs. The gene is either amplified or rearranged by chromosome translocation in these cell lines. We have isolated the mouse ortholog of this gene as well as a related gene (Abcp2) and are preparing to disrupt the gene to study its normal function. Characterization of additional expressed sequences from the human genome demonstrates that there are at least 45 ABC genes. Several of these genes are highly expressed in the liver and ovary and may play important roles in the transport/secretion of compounds from these organs. We previously demonstrated that alterations in the ABCR gene are associated with age-related macular degeneration (AMD), a common form of retinal degeneration that occurs in people over age 65. Establishment of an international cohort of centers allowed us to repeat this study on over 1400 cases and regionally matched controls. That data show that the G1961E variant confers a greater than 6-fold risk for AMD and the D2177N a greater than 3-fold risk. - ATP-binding cassette genes, chemotherapy, drug screening, multidrug resistance, - Human Tissues, Fluids, Cells, etc.
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