{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670318845185152.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.cmet.2007.03.009"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S1550413107000721?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S1550413107000721?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"17488636"}},{"identifier":{"@type":"NAID","@value":"30027522132"}}],"dc:title":[{"@value":"Molecular Pathogenesis of Pseudohypoaldosteronism Type II: Generation and Analysis of a Wnk4 Knockin Mouse Model"}],"description":[{"notation":[{"@value":"WNK1 and WNK4 mutations have been reported to cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder characterized by hyperkalemia and hypertension. To elucidate the molecular pathophysiology of PHAII, we generated Wnk4(D561A/+) knockin mice presenting the phenotypes of PHAII. The knockin mice showed increased apical expression of phosphorylated Na-Cl cotransporter (NCC) in the distal convoluted tubules. Increased phosphorylation of the kinases OSR1 and SPAK was also observed in the knockin mice. Apical localization of the ROMK potassium channel and transepithelial Cl(-) permeability in the cortical collecting ducts were not affected in the knockin mice, whereas activity of epithelial Na(+) channels (ENaC) was increased. This increase, however, was not evident after hydrochlorothiazide treatment, suggesting that the regulation of ENaC was not a genetic but a secondary effect. Thus, the pathogenesis of PHAII caused by a missense mutation of WNK4 was identified to be increased function of NCC through activation of the OSR1/SPAK-NCC phosphorylation cascade."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670318845185025","@type":"Researcher","foaf:name":[{"@value":"Sung-Sen Yang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185156","@type":"Researcher","foaf:name":[{"@value":"Tetsuji Morimoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185157","@type":"Researcher","foaf:name":[{"@value":"Tatemitsu Rai"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185159","@type":"Researcher","foaf:name":[{"@value":"Motoko Chiga"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185155","@type":"Researcher","foaf:name":[{"@value":"Eisei Sohara"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185026","@type":"Researcher","foaf:name":[{"@value":"Mayuko Ohno"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185154","@type":"Researcher","foaf:name":[{"@value":"Keiko Uchida"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185160","@type":"Researcher","foaf:name":[{"@value":"Shih-Hua Lin"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185152","@type":"Researcher","foaf:name":[{"@value":"Tetsuo Moriguchi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185024","@type":"Researcher","foaf:name":[{"@value":"Hiroshi Shibuya"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185153","@type":"Researcher","foaf:name":[{"@value":"Yoshiaki Kondo"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185027","@type":"Researcher","foaf:name":[{"@value":"Sei Sasaki"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318845185158","@type":"Researcher","foaf:name":[{"@value":"Shinichi Uchida"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"15504131"}],"prism:publicationName":[{"@value":"Cell Metabolism"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2007-05","prism:volume":"5","prism:number":"5","prism:startingPage":"331","prism:endingPage":"344"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license","http://www.elsevier.com/open-access/userlicense/1.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S1550413107000721?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S1550413107000721?httpAccept=text/plain"}],"createdAt":"2007-05-09","modifiedAt":"2025-10-27","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Physiology","dc:title":"Physiology"},{"@id":"https://cir.nii.ac.jp/all?q=Pseudohypoaldosteronism","dc:title":"Pseudohypoaldosteronism"},{"@id":"https://cir.nii.ac.jp/all?q=Genetic%20Vectors","dc:title":"Genetic Vectors"},{"@id":"https://cir.nii.ac.jp/all?q=HUMDISEASE","dc:title":"HUMDISEASE"},{"@id":"https://cir.nii.ac.jp/all?q=Mutation,%20Missense","dc:title":"Mutation, Missense"},{"@id":"https://cir.nii.ac.jp/all?q=Blood%20Pressure","dc:title":"Blood Pressure"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Biology","dc:title":"Cell Biology"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Serine-Threonine%20Kinases","dc:title":"Protein Serine-Threonine Kinases"},{"@id":"https://cir.nii.ac.jp/all?q=Urine","dc:title":"Urine"},{"@id":"https://cir.nii.ac.jp/all?q=Sodium%20Chloride%20Symporters","dc:title":"Sodium Chloride Symporters"},{"@id":"https://cir.nii.ac.jp/all?q=Disease%20Models,%20Animal","dc:title":"Disease Models, Animal"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Microscopy,%20Fluorescence","dc:title":"Microscopy, Fluorescence"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Phosphorylation","dc:title":"Phosphorylation"},{"@id":"https://cir.nii.ac.jp/all?q=Potassium%20Channels,%20Inwardly%20Rectifying","dc:title":"Potassium Channels, Inwardly Rectifying"},{"@id":"https://cir.nii.ac.jp/all?q=Epithelial%20Sodium%20Channels","dc:title":"Epithelial Sodium Channels"},{"@id":"https://cir.nii.ac.jp/all?q=Kidney%20Tubules,%20Distal","dc:title":"Kidney Tubules, Distal"},{"@id":"https://cir.nii.ac.jp/all?q=Molecular%20Biology","dc:title":"Molecular Biology"},{"@id":"https://cir.nii.ac.jp/all?q=Blood%20Chemical%20Analysis","dc:title":"Blood Chemical Analysis"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050005822275508096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK 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