ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 55 citations in OpenAlex.
- Structural and functional analysis of aquaporin-2 mutants involved in nephrogenic diabetes insipidus.Scientific reports · 2023Article
- Aquaporins in Diabetes Insipidus.Advances in experimental medicine and biology · 2023Article
- Aquaporins in Urinary System.Advances in experimental medicine and biology · 2023Article
- Molecular characterization of an aquaporin-2 mutation causing a severe form of nephrogenic diabetes insipidus.Cellular and molecular life sciences : CMLS · 2020Article
- Article
- Aquaporins in Renal Diseases.International journal of molecular sciences · 2019Review
- Angiotensin II Promotes KHypertension (Dallas, Tex. : 1979) · 2018Article
- Structural Basis for Mutations of Human Aquaporins Associated to Genetic Diseases.International journal of molecular sciences · 2018Article
- Hereditary Nephrogenic Diabetes Insipidus: Pathophysiology and Possible Treatment. An Update.International journal of molecular sciences · 2017Review
- AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A novel therapeutic effect of statins on nephrogenic diabetes insipidus.Journal of cellular and molecular medicine · 2015Review
- The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog.FEBS open bio · 2015Article
- Aquaporins: important but elusive drug targets.Nature reviews. Drug discovery · 2014Review
- Impaired surface expression and conductance of the KCNQ4 channel lead to sensorineural hearing loss.Journal of cellular and molecular medicine · 2013Article
- Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment.Endocrine reviews · 2013Review
- Functional polymorphisms affecting the clinically important arginine-137 residue of AVPR2 do not influence serum sodium concentration at the population level.Physiological genomics · 2013Article
- Distinct roles of molecular chaperones HSP90α and HSP90β in the biogenesis of KCNQ4 channels.PloS one · 2013Article
- Congenital nephrogenic diabetes insipidus: the current state of affairs.Pediatric nephrology (Berlin, Germany) · 2012Review
- Cell culture models and animal models for studying the patho-physiological role of renal aquaporins.Cellular and molecular life sciences : CMLS · 2012Review
- Regulation of transport in the connecting tubule and cortical collecting duct.Comprehensive Physiology · 2012Review
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3 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in aquaporin-2 (AQP2) that interfere with its cellular processing can produce autosomal recessive nephrogenic diabetes insipidus (NDI). Prior gene knock-in of the human NDI-causing AQP2 mutation T126M produced mutant mice that died by age 7 days. Here, we used a novel "conditional gene knock-in" strategy to generate adult, AQP2-T126M mutant mice. Mice separately heterozygous for floxed wild-type AQP2 and AQP2-T126M were bred to produce hemizygous mice, which following excision of the wild-type AQP2 gene by tamoxifen-induced Cre-recombinase gave AQP2(T126M/-) mice. AQP2(T126M/-) mice were polyuric (9-14 ml urine/day) compared to AQP2(+/+) mice (1.6 ml/day) and had reduced urine osmolality (400 vs. 1800 mosmol). Kidneys of AQP2(T126M/-) mice expressed core-glycosylated AQP2-T126M protein in an endoplasmic reticulum pattern. Screening of candidate protein folding "correctors" in AQP2-T126M-transfected kidney cells showed increased AQP2-T126M plasma membrane expression with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG increased urine osmolality in AQP2(T126M/-) mice by >300 mosmol but had no effect in AQP2(-/-) mice. Kidneys of 17-AAG-treated AQP2(T126M/-) mice showed partial rescue of defective AQP2-T126M cellular processing. Our results establish an adult mouse model of NDI and demonstrate partial restoration of urinary concentration function by a compound currently in clinical trials for other indications.
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