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This is this first in vivo proof of a long-standing hypothesis that comes from in vitro studies with recessive Aqp2 mutations. Transfection into MDCK cells of any of several Aqp2 mutations corresponding to recessive human alleles shows abnormal subcellular localization [25], [27] and failure to appropriately translocate to the plasma membrane. Thus, misfolding, retention in the ER, and failure to translocate in response to dDAVP were proposed as the mechanism for autosomal recessive NDI. Here we not only prove this hypothesis but also establish a useful model for human NDI. This mouse model of NDI based on an Aqp2 allele that can be rescued provides the opportunity to test therapies, including gene therapy, that may promote proper subcellular localization."}

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