{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T04:37:05Z","timestamp":1772080625587,"version":"3.50.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_173276\/1"],"award-info":[{"award-number":["310030_173276\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Centre of Competence in Research - Kidney.CH"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pflugers Arch - Eur J Physiol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The renal distal convoluted tubule (DCT) is critical for the fine-tuning of urinary ion excretion and the control of blood pressure. Ion transport along the DCT is tightly controlled by posttranscriptional mechanisms including a complex interplay of kinases, phosphatases, and ubiquitin ligases. Previous work\u00a0identified the transcription factor Prox-1 as a gene significantly enriched in the DCT of adult mice. To test if Prox-1 contributes to the transcriptional regulation of DCT function and structure, we developed a novel mouse model (NCC<jats:sup>cre<\/jats:sup>:Prox-1<jats:sup>flox\/flox<\/jats:sup>) for an inducible deletion of Prox-1 specifically in the DCT. The deletion of Prox-1 had no obvious impact on DCT structure and growth independent whether the deletion was achieved in newborn or adult mice. Furthermore, DCT-specific Prox-1 deficiency did not alter DCT-proliferation in response to loop diuretic treatment. Likewise, the DCT-specific deletion of Prox-1 did not cause other gross phenotypic abnormalities. Body weight, urinary volume, Na<jats:sup>+<\/jats:sup> and K<jats:sup>+<\/jats:sup> excretion as well as plasma Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>, and aldosterone levels were similar in Prox-1<jats:sub>DCT<\/jats:sub><jats:sup>KO<\/jats:sup> and Prox-1<jats:sub>DCT<\/jats:sub><jats:sup>Ctrl<\/jats:sup> mice. However, Prox-1<jats:sub>DCT<\/jats:sub><jats:sup>KO<\/jats:sup> mice exhibited a significant hypomagnesemia with a profound downregulation of the DCT-specific apical Mg<jats:sup>2+<\/jats:sup> channel TRPM6 and the NaCl cotransporter (NCC) at both mRNA and protein levels. The expression of other proteins involved in distal tubule Mg<jats:sup>2+<\/jats:sup> and Na<jats:sup>+<\/jats:sup> handling was not affected. Thus, Prox-1 is a DCT-enriched transcription factor that does not control DCT growth but contributes to the molecular control of DCT-dependent Mg<jats:sup>2+<\/jats:sup> homeostasis in the adult kidney.<\/jats:p>","DOI":"10.1007\/s00424-020-02491-1","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T17:04:54Z","timestamp":1605546294000},"page":"79-93","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Deletion of the transcription factor Prox-1 specifically in the renal distal convoluted tubule causes hypomagnesemia via reduced expression of TRPM6 and NCC"],"prefix":"10.1007","volume":"473","author":[{"given":"Christina","family":"Schnoz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Moser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise V.","family":"Kratschmar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Odermatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Loffing-Cueni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-6588","authenticated-orcid":false,"given":"Johannes","family":"Loffing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"2491_CR1","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1681\/ASN.2008060633","volume":"5","author":"S Adalat","year":"2009","unstructured":"Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van't Hoff W, Marks SD, Trompeter RS, Tullus K, Winyard PJ, Cansick J, Mushtaq I, Dhillon HK, Bingham C, Edghill EL, Shroff R, Stanescu H, Ryffel GU, Ellard S, Bockenhauer D (2009) HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 5:1123\u20131131","journal-title":"J Am Soc Nephrol"},{"issue":"1","key":"2491_CR2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00424-008-0601-7","volume":"458","author":"RJM Bindels","year":"2009","unstructured":"Bindels RJM, Hoenderop JG, Xi Q (2009) Regulation of magnesium reabsorption in DCT. Pflugers Arch - Eur J Physiol 458(1):89\u201398","journal-title":"Pflugers Arch - Eur J Physiol"},{"key":"2491_CR3","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1432-0436.2004.07207001.x","volume":"72","author":"M Bouchard","year":"2004","unstructured":"Bouchard M (2004) Transcriptional control of kidney development. Differentiation 72:295\u2013306","journal-title":"Differentiation"},{"key":"2491_CR4","doi-asserted-by":"crossref","first-page":"e20914","DOI":"10.7554\/eLife.20914","volume":"5","author":"V Chubanov","year":"2016","unstructured":"Chubanov V, Ferioli S, Wisnowsky A, Simmons DG, Leitzinger C, Einer C, Jonas W, Shymkiv Y, Bartsch H, Braun A, Akdogan B, Mittermeier L, Sytik L, Torben F, Jurinovic V, van der Vorst EP, Weber C, Yildirim \u00d6A, Sotlar K, Sch\u00fcrmann A, Zierler S, Zischka H, Ryazanov AG, Gudermann T (2016) Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival. Elife 5:e20914","journal-title":"Elife"},{"key":"2491_CR5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fasebj.2020.34.s1.06565","volume":"34","author":"RJ Cornelius","year":"2020","unstructured":"Cornelius RJ, Sharma A, Su X, McMahon AP, Ellison DH, McCormick JA (2020) A novel distal convoluted tubule-specific tamoxifen-inducible Cre-recombinase driven by the NaCl cotransporter gene. FASEB J 34:1\u20131","journal-title":"FASEB J"},{"key":"2491_CR6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1152\/physrev.2001.81.1.51","volume":"81","author":"LJ Dai","year":"2001","unstructured":"Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, Quamme GA (2001) Magnesium transport in the renal distal convoluted tubule. Physiol Rev 81:51\u201384","journal-title":"Physiol Rev"},{"key":"2491_CR7","doi-asserted-by":"crossref","first-page":"F1563","DOI":"10.1152\/ajprenal.00322.2013","volume":"11","author":"JH De Baaij","year":"2013","unstructured":"De Baaij JH, Groot Koerkamp MJ, Lavrijsen M, van Zeeland F, Meijer H, Holstege FC, Bindels RJ, Hoenderop JG (2013) Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg(2+) handling. Am J Physiol Renal Physiol 11:F1563\u2013F1573","journal-title":"Am J Physiol Renal Physiol"},{"key":"2491_CR8","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ng1144","volume":"34","author":"MA Dyer","year":"2003","unstructured":"Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet 34:53\u201358","journal-title":"Nat Genet"},{"key":"2491_CR9","doi-asserted-by":"crossref","first-page":"F616","DOI":"10.1152\/ajprenal.2000.279.4.F616","volume":"279","author":"DH Ellison","year":"2000","unstructured":"Ellison DH (2000) Divalent cation transport by the distal nephron: insights from Bartter\u2019s and Gitelman\u2019s syndromes. Am J Physiol Renal Physiol 279:F616\u2013F625","journal-title":"Am J Physiol Renal Physiol"},{"key":"2491_CR10","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s10555-012-9390-8","volume":"31","author":"T Elsir","year":"2012","unstructured":"Elsir T, Smits A, Lindstrom MS, Nister M (2012) Transcription factor PROX1: its role in development and cancer. Cancer Metastasis Rev 31:793\u2013805","journal-title":"Cancer Metastasis Rev"},{"key":"2491_CR11","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1139\/Y10-080","volume":"88","author":"M Glover","year":"2010","unstructured":"Glover M, Mercier Zuber A, Figg N, O'Shaughnessy KM (2010) The activity of the thiazide-sensitive Na(+)-Cl(-) cotransporter is regulated by protein phosphatase PP4. Can J Physiol Pharmacol 88:986\u2013995","journal-title":"Can J Physiol Pharmacol"},{"key":"2491_CR12","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1681\/ASN.2005030314","volume":"17","author":"J Hadchouel","year":"2006","unstructured":"Hadchouel J, Delaloy C, Faure S, Achard JM, Jeunemaitre X (2006) Familial hyperkalemic hypertension. J Am Soc Nephrol 17:208\u2013217","journal-title":"J Am Soc Nephrol"},{"key":"2491_CR13","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev-physiol-021115-105431","volume":"78","author":"J Hadchouel","year":"2016","unstructured":"Hadchouel J, Ellison DH, Gamba G (2016) Regulation of renal electrolyte transport by WNK and SPAK-OSR1 kinases. Annu Rev Physiol 78:367\u2013389","journal-title":"Annu Rev Physiol"},{"key":"2491_CR14","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/ng1642","volume":"37","author":"NL Harvey","year":"2005","unstructured":"Harvey NL, Srinivasan RS, Dillard ME, Johnson NC, Witte MH, Boyd K, Sleeman MW, Oliver G (2005) Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat Genet 37:1072\u20131081","journal-title":"Nat Genet"},{"key":"2491_CR15","doi-asserted-by":"publisher","first-page":"260159","DOI":"10.1155\/2015\/260159","volume":"2015","author":"EV Ignatieva","year":"2015","unstructured":"Ignatieva EV, Levitsky VG, Kolchanov NA (2015) Human genes encoding transcription factors and chromatin-modifying proteins have low levels of promoter polymorphism: a study of 1000 genomes project data. Int J Genomics 2015:260159\u2013260115. https:\/\/doi.org\/10.1155\/2015\/260159","journal-title":"Int J Genomics"},{"issue":"12","key":"2491_CR16","volume":"10","author":"K Kato","year":"2015","unstructured":"Kato K, Konno D, Berry M, Matsuzaki F, Logan A, Hidalgo A (2015) Prox1 inhibits proliferation and is required for differentiation of the oligodendrocyte cell lineage in the mouse. PLoS One 10(12):e0145334","journal-title":"PLoS One"},{"key":"2491_CR17","unstructured":"Kim YM, Kim WY, Nam SA, Choi AR, Kim H, Kim YK, Kim HS, Kim J (2015) Role of Prox1 in the transforming ascending thin limb of Henle\u2019s loop during mouse kidney development. PLoS One e0127429"},{"key":"2491_CR18","doi-asserted-by":"crossref","first-page":"13124","DOI":"10.1038\/ncomms13124","volume":"7","author":"R Kivel\u00e4","year":"2016","unstructured":"Kivel\u00e4 R, Salmela I, Nguyen Y, Petrova TV, Koistinen HA, Wiener Z, Alitalo K (2016) The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation. Nat Commun 7:13124","journal-title":"Nat Commun"},{"key":"2491_CR19","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.kint.2017.03.034","volume":"5","author":"A Kompatscher","year":"2017","unstructured":"Kompatscher A, de Baaij JHF, Aboudehen K, Hoefnagels APWM, Igarashi P, Bindels RJM, Veenstra GJC, Hoenderop JGJ (2017) Loss of transcriptional activation of the potassium channel Kir5.1 by HNF1\u03b2 drives autosomal dominant tubulointerstitial kidney disease. Kidney Int 5:1145\u20131156","journal-title":"Kidney Int"},{"issue":"suppl 4","key":"2491_CR20","doi-asserted-by":"crossref","first-page":"iv63","DOI":"10.1093\/ndt\/gfu198","volume":"29","author":"M Konrad","year":"2014","unstructured":"Konrad M, Schlingmann KP (2014) Inherited disorders of renal hypomagnesaemia. Nephrol Dial Transplant 29(suppl 4):iv63\u2013iv71","journal-title":"Nephrol Dial Transplant"},{"key":"2491_CR21","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1093\/oxfordjournals.aje.a114186","volume":"122","author":"L Kuller","year":"1985","unstructured":"Kuller L, Farrier N, Caggiula A, Borhani N, Dunkle S (1985) Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Factor Intervention Trial. Am J Epidemiol 122:1045\u20131059","journal-title":"Am J Epidemiol"},{"key":"2491_CR22","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.cell.2018.01.029","volume":"172","author":"SA Lambert","year":"2018","unstructured":"Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, Chen X, Taipale J, Hughes TR, Weirauch MT (2018) The human transcription factors. Cell 172:650\u2013665","journal-title":"Cell"},{"key":"2491_CR23","first-page":"2669","volume":"11","author":"JW Lee","year":"2015","unstructured":"Lee JW, Chou CL, Knepper MA (2015) Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J Am Soc Nephrol 11:2669\u20132677","journal-title":"J Am Soc Nephrol"},{"issue":"6","key":"2491_CR24","doi-asserted-by":"crossref","first-page":"F1021","DOI":"10.1152\/ajprenal.0085.2001","volume":"281","author":"J Loffing","year":"2001","unstructured":"Loffing J, Loffing-Cueni D, Valderrabano V, Kl\u00e4usli L, Hebert SC, Rossier BC, Hoenderop JG, Bindels RJ, Kaissling B (2001) Distribution of transcellular calcium and sodium transport pathways along mouse distal nephron. Am J Physiol Renal Physiol 281(6):F1021\u2013F1027","journal-title":"Am J Physiol Renal Physiol"},{"key":"2491_CR25","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1097\/01.ASN.0000138234.18569.63","volume":"15","author":"J Loffing","year":"2004","unstructured":"Loffing J, Vallon V, Loffing-Cueni D, Aregger F, Richter K, Pietri L, Bloch-Faure M, Hoenderop JG, Shull GE, Meneton P, Kaissling B (2004) Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman\u2019s syndrome. J Am Soc Nephrol 15:2276\u20132288","journal-title":"J Am Soc Nephrol"},{"key":"2491_CR26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nn.2467","volume":"13","author":"L Madisen","year":"2010","unstructured":"Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR, Lein ES, Zeng H (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13:133\u2013140","journal-title":"Nat Neurosci"},{"key":"2491_CR27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14814\/phy2.13843","volume":"6","author":"H Mayan","year":"2018","unstructured":"Mayan H, Farfel Z, Karlish SJD (2018) Renal Mg handling, FXYD2 and the central role of the Na,K-ATPase. Physiol Rep 6:1\u201310","journal-title":"Physiol Rep"},{"key":"2491_CR28","first-page":"45","volume":"5","author":"JA McCormick","year":"2015","unstructured":"McCormick JA, Ellison DH (2015) Distal convoluted tubule. Compr Physiol 5:45\u201398","journal-title":"Compr Physiol"},{"key":"2491_CR29","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/81543","volume":"26","author":"IC Meij","year":"2000","unstructured":"Meij IC, Koenderink JB, van Bokhoven H, Assink KF, Groenestege WT, de Pont JJ, Bindels RJ, Monnens LA, van den Heuvel LP, Knoers NV (2000) Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit. Nat Genet 26:265\u2013266","journal-title":"Nat Genet"},{"key":"2491_CR30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00424-013-1407-9","volume":"466","author":"AD Moes","year":"2014","unstructured":"Moes AD, van der Lubbe N, Zietse R, Loffing J, Hoorn EJ (2014) The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation. Pflugers Arch - Eur J Physiol 466:107\u2013118","journal-title":"Pflugers Arch - Eur J Physiol"},{"key":"2491_CR31","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1172\/JCI24134","volume":"115","author":"T Nijenhuis","year":"2005","unstructured":"Nijenhuis T, Vallon V, van der Kemp AW, Loffing J, Hoenderop JG, Bindels RJ (2005) Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest 115:1651\u20131658","journal-title":"J Clin Invest"},{"issue":"1","key":"2491_CR32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0925-4773(93)90012-M","volume":"44","author":"G Oliver","year":"1993","unstructured":"Oliver G, Sosa-Pineda B, Geisendorf S, Spana EP, Doe CQ, Gruss P (1993) Prox1, a prospero-related homeobox gene expressed during mouse development. Mech Dev 44(1):3\u201316","journal-title":"Mech Dev"},{"key":"2491_CR33","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1681\/ASN.2012121202","volume":"25","author":"N Picard","year":"2014","unstructured":"Picard N, Trompf K, Yang CL, Miller RL, Carrel M, Loffing-Cueni D, Fenton RA, Ellison DH, Loffing J (2014) Protein phosphatase 1 inhibitor-1 deficiency reduces phosphorylation of renal NaCl cotransporter and causes arterial hypotension. J Am Soc Nephrol 25:511\u2013522","journal-title":"J Am Soc Nephrol"},{"key":"2491_CR34","first-page":"657","volume":"123","author":"C Ronzaud","year":"2013","unstructured":"Ronzaud C, Loffing-Cueni D, Hausel P, Debonneville A, Malsure SR, Fowler-Jaeger N, Boase NA, Perrier R, Maillard M, Yang B, Stokes JB, Koesters R, Kumar S, Hummler E, Loffing J, Staub O (2013) Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension. J Clin Invest 123:657\u2013665","journal-title":"J Clin Invest"},{"issue":"suppl1","key":"2491_CR35","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2165\/00003495-198400281-00017","volume":"28","author":"MP Ryan","year":"1984","unstructured":"Ryan MP, Devane J, Ryan MF, Counihan TB (1984) Effects of diuretics on the renal handling of magnesium. Drugs 28(suppl1):167\u2013181","journal-title":"Drugs"},{"key":"2491_CR36","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ng889","volume":"31","author":"K Schlingmann","year":"2002","unstructured":"Schlingmann K, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D, Syrrou M, Nielsen S, Sassen M, Waldegger S, Seyberth W, Konrad M (2002) Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 31:166\u2013170","journal-title":"Nat Genet"},{"issue":"3","key":"2491_CR37","doi-asserted-by":"crossref","first-page":"F367","DOI":"10.1152\/ajprenal.1999.276.3.F367","volume":"276","author":"R Schmitt","year":"1999","unstructured":"Schmitt R, Ellison DH, Farman N, Rossier BC, Reilly RF, Reeves WB, Oberb\u00e4umer I, Tapp R, Bachmann S (1999) Developmental expression of sodium entry pathways in rat nephron. Am J Physiol Renal Physiol 276(3):F367\u2013F381","journal-title":"Am J Physiol Renal Physiol"},{"key":"2491_CR38","doi-asserted-by":"publisher","unstructured":"Schnoz C, Carrel M, Loffing J (2020) Loss of NCC impairs the outgrowth of the renal distal convoluted tubule, Nephrol Dial Transpl gfz172, https:\/\/doi.org\/10.1093\/ndt\/gfz172","DOI":"10.1093\/ndt\/gfz172"},{"key":"2491_CR39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/jbc.273.44.29150","volume":"273","author":"PJ Schultheis","year":"1998","unstructured":"Schultheis PJ, Lorenz JN, Meneton P, Niema ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML, Sholl GE (1998) Phenotype resembling Gitelman\u2019s syndrome in mice lacking the apical Na+-Cl- cotransporter of the distal convoluted tubule. J Biol Chem 273:1\u20136","journal-title":"J Biol Chem"},{"key":"2491_CR40","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng0196-24","volume":"12","author":"DB Simon","year":"1996","unstructured":"Simon DB, Nelson-Williams C, Johnson Bia M, Ellison D, Karet FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ, Gitelman HJ, Lifton RP (1996) Gitelman\u2019s variant of Bartter\u2019s syndrome, inherited hypokalaemic alkalosis, is caused by mutation sin the thiazide-sensitive NaCl cotransporter. Nat Genet 12:24\u201330","journal-title":"Nat Genet"},{"key":"2491_CR41","first-page":"1417","volume":"9","author":"E Sohara","year":"2015","unstructured":"Sohara E, Uchida S (2015) Kelch-like 3\/Cullin 3 ubiquitin ligase complex and WNK signaling in salt-sensitive hypertension and electrolyte disorder. Nephrol Dial Transplant 9:1417\u20131424","journal-title":"Nephrol Dial Transplant"},{"issue":"3","key":"2491_CR42","doi-asserted-by":"publisher","first-page":"12374","DOI":"10.1111\/jne.12374","volume":"28","author":"P Strajhar","year":"2016","unstructured":"Strajhar P, Schmid Y, Liakoni E, Dolder PC, Rentsch KM, Kratschmar DV, Odermatt A, Liechti ME (2016) Acute effects of lysergic acid diethylamide on circulating steroid levels in healthy subjects. J Neuroendocrinol 28(3):12374. https:\/\/doi.org\/10.1111\/jne.12374","journal-title":"J Neuroendocrinol"},{"key":"2491_CR43","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1681\/ASN.2008030327","volume":"20","author":"S Thebault","year":"2009","unstructured":"Thebault S, Alexander RT, Tiel Groenestege WM, Hoenderop JG, Bindels RJ (2009) EGF increases TRPM6 activity and surface expression. J Am Soc Nephrol 20:78\u201385","journal-title":"J Am Soc Nephrol"},{"issue":"5","key":"2491_CR44","doi-asserted-by":"crossref","first-page":"F901","DOI":"10.1152\/ajprenal.00286.2016","volume":"311","author":"F Trepiccione","year":"2016","unstructured":"Trepiccione F, Soukaseum C, Iervolino A, Petrillo F, Zacchia M, Schutz G, Eladari D, Capasso G, Hadchouel J (2016) A fate-mapping approach reveals the composite origin of the connecting tubule and alerts on \u201csingle-cell\u201d-specific KO model of the distal nephron. Am J Physiol Renal Physiol 311(5):F901\u2013F906","journal-title":"Am J Physiol Renal Physiol"},{"issue":"3","key":"2491_CR45","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1152\/physrev.00008.2018","volume":"99","author":"J Van der Wijst","year":"2019","unstructured":"Van der Wijst J, Belge H, Bindels RJM, Devuyst O (2019) Learning physiology from inherited kidney disorders. Physiol Rev 99(3):1575\u20131653","journal-title":"Physiol Rev"},{"key":"2491_CR46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1074\/jbc.M311201200","volume":"279","author":"T Voets","year":"2004","unstructured":"Voets T, Nilius B, Hoefs S, van der Kemp AW, Droogmans G, Bindels RJ, Hoenderop JG (2004) TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 279:19\u201325","journal-title":"J Biol Chem"},{"key":"2491_CR47","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00424-003-1082-3","volume":"446","author":"CA Wagner","year":"2003","unstructured":"Wagner CA, L\u00fckewille U, Valles P, Breton S, Brown D, Giebisch GH, Geibel JP (2003) A rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse. Pflugers Arch - Eur J Physiol 446:623\u2013632","journal-title":"Pflugers Arch - Eur J Physiol"},{"key":"2491_CR48","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng901","volume":"31","author":"R Walder","year":"2002","unstructured":"Walder R, Landau D, Meyer P, Shalev H, Tsolia M, Borochowitz Z, Boettger MB, Beck GE, Engelhardt RK, Carmi R, Sheffield VC (2002) Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet 31:171\u2013174","journal-title":"Nat Genet"},{"issue":"6","key":"2491_CR49","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0092-8674(00)81511-1","volume":"98","author":"JT Wigle","year":"1999","unstructured":"Wigle JT, Oliver G (1999) Prox1 function is required for the development of the murine lymphatic system. Cell 98(6):769\u2013778","journal-title":"Cell"},{"key":"2491_CR50","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/6844","volume":"21","author":"JT Wigle","year":"1999","unstructured":"Wigle JT, Chowdhury K, Gruss P, Oliver G (1999) Prox1 function is crucial for mouse lens-fibre elongation. Nat Genet 21:318\u2013322","journal-title":"Nat Genet"},{"key":"2491_CR51","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1126\/science.1062844","volume":"293","author":"FH Wilson","year":"2001","unstructured":"Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP (2001) Human hypertension caused by mutations in WNK kinases. Science 293:1107\u20131112","journal-title":"Science"}],"container-title":["Pfl\u00fcgers Archiv - European Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-020-02491-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00424-020-02491-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-020-02491-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T14:20:22Z","timestamp":1609770022000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00424-020-02491-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,16]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["2491"],"URL":"https:\/\/doi.org\/10.1007\/s00424-020-02491-1","relation":{},"ISSN":["0031-6768","1432-2013"],"issn-type":[{"value":"0031-6768","type":"print"},{"value":"1432-2013","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,16]]},"assertion":[{"value":"14 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}