Tissue-specific expression of the ABCC6 gene

The ABCC6 gene encodes MRP6, a member of the multidrug resistance-associated protein (MRP) family. Interest in ABCC6/MRP6 derives, in part, from the fact that mutations in this gene/protein system have been identified in families with pseudoxanthoma elasticum (PXE). Early studies indicated that ABCC6 is expressed primarily in the liver and to a lesser extent in the kidney, but more recently a widespread distribution has been suggested. To explore the tissue-specific expression of ABCC6, we first examined various mouse tissues by RT-PCR. The results indicated high levels of mRNA in the liver, whereas low level of expression was noted in the kidney and small intestine. To explore other tissues in which initial RT-PCR was essentially negative, a second-round nested PCR was performed, which revealed expression also in the brain, tongue, stomach, and eye. Unexpectedly, however, distinct PCR products of smaller molecular weight were noted in these tissues. Subcloning and sequencing of these PCR products indicated that they reflected aberrant splicing in the 3' end of the ABCC6 mRNA, resulting in each case in a premature termination codon. Similar results were noted with RT-PCR analysis using RNA isolated from cultured human epidermal keratinocytes and dermal fibroblasts. Collectively, our results confirm high level of expression of ABCC6 in the liver and the kidney, whereas very low level of expression in a variety of other tissues was noted. The results have implications for mutation detection strategies in PXE by RT-PCR, and they further support the notion that PXE is a primary metabolic disorder.