Studies on the physiological roles of intracellular OLO chloride channels

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1) We generated transgenic mice expressing GFP under the control of CLC-KB gene promoter. It clearly determined the sites of intrarenal expression of CLC-KB.2) We generated CLC-3 KO mice, and found that CLC-3 is functioning in intracellular acidic organelles, and that it is involved in protein-degradation pathways.3) We successfully isolated fish CLC-K channel. This provided us information on the ancient role of CLC-K channels.4) We determined the molecular pathogenesis of Bartter's syndrome by barttin mutations in mammalian cells. In immunocytochemistry, CLC-K2 was retained in the Golgi in the absence of barttin expression, but delivered to the plasma membrane when barttin was present. Bartlin was co-precipitated with CLC-K2, suggesting a protein-protein interaction. Disease-causing mutant barttins, especially R8L, were retained intracellularly, but their binding ability to CLC-K2 was preserved. This led to a retention of CLC-K2 in intracellular organelles with barttin, and a loss of plasma membrane localization.