Abstract
In kidney, various types of channels and transporters present in the specific nephron segments are functioning to maintain body fluid balance. Mutations of these membrane proteins have been found to cause some human genetic diseases, such as Bartter syndrome and nephrogenic diabetes insipidus (NDI). These naturally occurring mutations sometimes tell us important functional domains within proteins, especially in terms of protein sorting. Recently, we found three frame-shift mutations in the AQP2 gene in patients having autosomal dominant (AD)-type NDI. Previously, we have demonstrated that the AQP2 (763-772 del), a 10 nucleotide-deletion mutant, was mis-localized to the basolateral membrane in MDCK cells. To analyze this sorting abnormality in vivo, we created AQP2 (763-772 del) knock-in mice, which showed severely impaired urine concentrating ability. Using this mouse model, we will discuss the molecular pathogenesis of AD-NDI in vivo, and also the usefulness of knock-in mouse models in the study of transportsome. [J Physiol Sci. 2006;56 Suppl:S10]
