Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation
Nephrogenic diabetes insipidus
Aquaporin 2
Compound heterozygosity
DOI:
10.1073/pnas.0602331103
Publication Date:
2006-09-13T02:25:03Z
AUTHORS (10)
ABSTRACT
Frame-shift mutations within the C terminus of aquaporin 2 (AQP2) cause autosomal-dominant nephrogenic diabetes insipidus (AD-NDI). To identify molecular mechanism(s) this disease in vivo and to test possible therapeutic strategies, we generated a mutant AQP2 (763–772 del) knockin mouse. Heterozygous mice showed severely impaired urine-concentrating ability. However, they were able slightly increase urine osmolality after dehydration. This milder phenotype, when compared with autosomal-recessive NDI, is feature AD-NDI humans, thus suggesting successful establishment an mouse model. Immunofluorescence collecting duct cells revealed that was missorted basolateral instead apical plasma membrane. Furthermore, formed heterooligomer wild-type dominant-negative effect on normal sorting even under Using mouse, tested several drugs for treatment found rolipram, phosphodiesterase 4 inhibitor, osmolality. Phosphodiesterase inhibitors may be useful AD-NDI. animal model demonstrates monomer gains reverses polarized multimers.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (23)
CITATIONS (86)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....