抄録
Kidney is the most important organ for water and electrolytes metabolism within body. This process is mostly attained by numerous water and electrolytes transport systems automatically regulated in response to ever changing external conditions. Recently, some of the disturbances of water and electrolytes metabolism were identified to be caused by the mutations of specific renal transporters and channels. However, identification of a responsible gene does not always guarantee that molecular pathogenesis of the disease is fully understood. In addition, naturally occurring mutations often tell us important functional domains of the protein of our interest and its regulatory mechanism. Accordingly, functional analysis of disease-causing mutants is important for understanding pathophysiological roles of channels and transporters. However, it has been hampered by the lack of good cell lines endogenously expressing these proteins. To overcome this situation, we generated AQP2 water channel and WNK4 kinase knock-in mice to study molecular pathogenesis of autosomal dominant type nephrogenic diabetes insipidus (AD-NDI) and pseudohypoaldoseronism type II (PHAII), respectively. Analysis of these mice revealed novel molecular mechanisms of the diseases. In addition, these mice were good resources for further studies using proteomics techniques and also for testing possible therapeutic strategies for the diseases. [J Physiol Sci. 2007;57 Suppl:S42]
