Aquaporin gene delivery to kidney.
Aquaporin gene delivery to kidney.BACKGROUND: Several aquaporin- ( AQP) type water channels are expressed in kidney tubules and microvessels, including AQP1 in proximal tubule, thin descending limb of Henle and vasa recta, AQP2 in collecting duct apical membrane, and AQP3 and AQP4 in collecting duct basolateral membrane. Mice deficient in these aquaporins have distinct phenotypic abnormalities. AQP1 null mice are polyuria and unable to generate a concentrated urine after water deprivation. AQP2-T126M mutant mice and AQP3 null mice manifest nephrogenic diabetes insipidus (NDI) with severe polyuria, whereas AQP4 null mice have only a mild defect in maximal urinary concentrating ability. We reasoned that these mice could serve as useful models for gene replacement because of their predictable and unambiguous phenotypes.METHODS: In an initial feasibility study, an adenovirus directing the expression of AQP1 was introduced into AQP1 null mice by intravenous infusion.RESULTS: At 1 week after adenovirus infusion, AQP1 was seen in many proximal tubules and microvessels. Compared with untreated null mice, the treated mice were able to partially concentrate their urine and lost less weight after water deprivation. However, AQP1 transgene expression and functional correction were lost over 3-5 weeks.CONCLUSION: Although there remain many technical problems to overcome, aquaporin gene replacement has potential applications in hereditary and acquired NDI, and in the transient modulation of renal fluid conservation.[1]References
- Aquaporin gene delivery to kidney. Verkman, A.S., Yang, B. Kidney Int. (2002) [Pubmed]
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