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We generated and analyzed\n                    <jats:italic>Klhl3<\/jats:italic>\n                    knock\u2010in (KI) mice carrying a missense\n                    <jats:italic>M131V<\/jats:italic>\n                    mutation in the BTB domain (corresponding to human\n                    <jats:italic>KLHL3 M78V<\/jats:italic>\n                    mutation).\n                    <jats:italic>\n                      Klhl3\n                      <jats:sup>M131V\/+<\/jats:sup>\n                    <\/jats:italic>\n                    KI mice exhibited typical PHAII phenotype with an exaggerated diuretic response to hydrochlorothiazide. Their kidney tissues showed an unchanged KLHL3, decreased cullin 3 (Cul3), and increased with\u2010no\u2010lysine kinases (WNKs) WNK1 and WNK4 along with an enhanced downstream ste20\u2010related proline\/alanine\u2010rich kinase\/oxidative stress response kinase 1\u2010N(K)CC phosphorylation. Their Cul3 protein in the cytosol of distal convoluted tubule cells was also significantly attenuated on immunogold\u2010labeling electron microscopy. In micro\u2010dissected renal tubules,\n                    <jats:italic>\n                      Klhl3\n                      <jats:sup>M131V\/+<\/jats:sup>\n                    <\/jats:italic>\n                    KI mice expressed high levels of\n                    <jats:italic>Wnk4 mRNA<\/jats:italic>\n                    in the distal nephron.\n                    <jats:italic>In vitro<\/jats:italic>\n                    coimmunoprecipitation showed the\n                    <jats:italic>KLHL3<\/jats:italic>\n                    BTB domain mutation retained intact interaction with WNKs but reduced binding to Cul3, thus leading to the increased abundance of total WNKs. In summary,\n                    <jats:italic>\n                      Klhl3\n                      <jats:sup>M131V\/+<\/jats:sup>\n                    <\/jats:italic>\n                    KI mice feature typical PHAII with a simultaneous increase of WNK1 and WNK4 through the impaired KLHL3 BTB domain binding to Cul3.\u2014Lin, C.\u2010M., Cheng, C.\u2010J., Yang, S.\u2010S., Tseng, M.\u2010H., Yen, M.\u2010T., Sung, C.\u2010C., Lin, S.\u2010H. Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by\n                    <jats:italic>KLHL3<\/jats:italic>\n                    mutation in BTB domain. FASEB J. 33, 1051\u20131061 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801023r","type":"journal-article","created":{"date-parts":[[2018,8,27]],"date-time":"2018-08-27T13:40:31Z","timestamp":1535377231000},"page":"1051-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by\n                    <i>KLHL3<\/i>\n                    mutation in BTB domain"],"prefix":"10.1096","volume":"33","author":[{"given":"Chien-Ming","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences Tri-Service General Hospital National Defense Medical Center  Taipei Taiwan"},{"name":"Department of Pediatrics Tri-Service General Hospital National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Jen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Tri-Service General Hospital National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences Tri-Service General Hospital National Defense Medical Center  Taipei Taiwan"},{"name":"Division of Nephrology Department of Medicine Tri-Service General Hospital National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hua","family":"Tseng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences Tri-Service General Hospital National Defense Medical Center  Taipei Taiwan"},{"name":"Division of Pediatric Nephrology Department of 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