Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum
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Multidrug resistance protein 4 (MRP4) is a transmembrane efflux protein capable of substrate-specific transport of endogenous and xenobiotic molecules across the cell membrane, including several drugs used in disease and cancer treatment. Changes in expression of MRP4 affect bioavailability and efficacy of treatment drugs. Expression changes also affect intracellular and extracellular levels of substrate molecules that participate in secondary messenger pathways (e.g. cAMP). The MRP4 (ABCC4) gene is highly polymorphic in the human population, and polymorphisms alter the function and expression of the protein. The aim of this study was to conduct a large-scale proteomic analysis of Mrp4 deficient mice to test if levels of other proteins and small molecules are altered in the absence of MRP4. This study focuses on protein expression in liver, kidney, brain and serum by utilizing proprietary multi-analyte profiling platforms at MyriadRBM (Austin, TX). Eight analytes in kidney, two in serum and one in liver were found to be significantly different in six-month old C57BL/6-Mrp4 knockout mice. The changes are suggestive of tissue repair and inflammation in the kidney. These data suggest potential adverse effects due to the absence of MRP4.