{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:57:54Z","timestamp":1791536274144,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Claudins are key components of the tight junction, sealing the paracellular cleft or composing size-, charge- and water-selective paracellular channels. Claudin-10 occurs in two major isoforms, claudin-10a and claudin-10b, which constitute paracellular anion or cation channels, respectively. For several years after the discovery of claudin-10, its functional relevance in men has remained elusive. Within the past two years, several studies appeared, describing patients with different pathogenic variants of the CLDN10 gene. Patients presented with dysfunction of kidney, exocrine glands and skin. This review summarizes and compares the recently published studies reporting on a novel autosomal-recessive disorder based on claudin-10 mutations.<\/jats:p>","DOI":"10.3390\/ijms20215396","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"5396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A Novel Claudinopathy Based on Claudin-10 Mutations"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9893-0473","authenticated-orcid":false,"given":"Susanne","family":"Milatz","sequence":"first","affiliation":[{"name":"Institute of Physiology, Kiel University, Christian-Albrechts-Platz 4, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1172\/JCI12464","article-title":"Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability","volume":"107","author":"Rahner","year":"2001","journal-title":"J. Clin. Invest."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1083\/jcb.153.2.263","article-title":"Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells","volume":"153","author":"Furuse","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1083\/jcb.200110122","article-title":"Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice","volume":"156","author":"Furuse","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1242\/jcs.00165","article-title":"Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells","volume":"115","author":"Amasheh","year":"2002","journal-title":"J. Cell. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"C142","DOI":"10.1152\/ajpcell.00038.2002","article-title":"Claudins create charge-selective channels in the paracellular pathway between epithelial cells","volume":"283","author":"Colegio","year":"2002","journal-title":"Am. J. Physiol., Cell Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1083\/jcb.200302070","article-title":"Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice","volume":"161","author":"Nitta","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"F1078","DOI":"10.1152\/ajprenal.00116.2003","article-title":"Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins","volume":"285","author":"Fanning","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17350","DOI":"10.1074\/jbc.M213286200","article-title":"Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation","volume":"278","author":"Yu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00441-005-1101-0","article-title":"Contribution of claudin-5 to barrier properties in tight junctions of epithelial cells","volume":"321","author":"Amasheh","year":"2005","journal-title":"Cell Tissue Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F1288","DOI":"10.1152\/ajprenal.00138.2006","article-title":"Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities","volume":"291","author":"Rogan","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00232-007-9014-3","article-title":"Claudin-8 expression in renal epithelial cells augments the paracellular barrier by replacing endogenous claudin-2","volume":"215","author":"Angelow","year":"2007","journal-title":"J. Membr. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1242\/jcs.040113","article-title":"Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function","volume":"122","author":"Stuiver","year":"2009","journal-title":"J. Cell. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1242\/jcs.060665","article-title":"Claudin-2, a component of the tight junction, forms a paracellular water channel","volume":"123","author":"Rosenthal","year":"2010","journal-title":"J. Cell. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.bbamem.2010.07.014","article-title":"Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes","volume":"1798","author":"Milatz","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1053\/j.gastro.2010.08.006","article-title":"Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine","volume":"140","author":"Tamura","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1007\/s00018-012-0949-x","article-title":"Claudin-17 forms tight junction channels with distinct anion selectivity","volume":"69","author":"Krug","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1128\/MCB.00758-15","article-title":"Claudin-21 Has a Paracellular Channel Role at Tight Junctions","volume":"36","author":"Tanaka","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rosenthal, R., G\u00fcnzel, D., Piontek, J., Krug, S.M., Ayala-Torres, C., Hempel, C., Theune, D., and Fromm, M. (2019). Claudin-15 forms a water channel through the tight junction with distinct function compared to claudin-2. Acta Physiol (Oxf), e13334.","DOI":"10.1111\/apha.13334"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ejcb.2010.01.003","article-title":"The protoplasmic or exoplasmic face association of tight junction particles cannot predict paracellular permeability or heterotypic claudin compatibility","volume":"89","author":"Inai","year":"2010","journal-title":"Eur. J. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1679\/aohc.68.349","article-title":"Heterogeneity in expression and subcellular localization of tight junction proteins, claudin-10 and -15, examined by RT-PCR and immunofluorescence microscopy","volume":"68","author":"Inai","year":"2005","journal-title":"Arch. Histol. Cytol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00424-015-1748-7","article-title":"Corticomedullary difference in the effects of dietary Ca2+ on tight junction properties in thick ascending limbs of Henle\u2019s loop","volume":"468","author":"Plain","year":"2016","journal-title":"Pflugers Arch."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E219","DOI":"10.1073\/pnas.1611684114","article-title":"Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na + and Mg 2+ transport","volume":"114","author":"Milatz","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1038\/emboj.2012.49","article-title":"Claudin-14 regulates renal Ca++ transport in response to CaSR signalling via a novel microRNA pathway","volume":"31","author":"Gong","year":"2012","journal-title":"EMBO J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1681\/ASN.2014111067","article-title":"Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment-Specific Transcriptomes","volume":"26","author":"Lee","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14241","DOI":"10.1073\/pnas.1203834109","article-title":"Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis","volume":"109","author":"Breiderhoff","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Seker, M., Fernandez-Rodriguez, C., Martinez-Cruz, L.A., and M\u00fcller, D. (2019). Mouse models of human claudin-associated disorders: benefits and limitations. Int. J. Mol. Sci., submitted for publication.","DOI":"10.3390\/ijms20215504"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/sj.ejhg.5200475","article-title":"Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene","volume":"8","author":"Weber","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(01)00200-8","article-title":"Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29","volume":"104","author":"Wilcox","year":"2001","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1053\/j.gastro.2004.07.022","article-title":"Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease","volume":"127","author":"Baala","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/ng.404","article-title":"Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density","volume":"41","author":"Thorleifsson","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1086\/508617","article-title":"Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement","volume":"79","author":"Konrad","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1172\/JCI26323","article-title":"Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16","volume":"116","author":"Kausalya","year":"2006","journal-title":"J. Clin. Invest."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng0696-183","article-title":"Bartter\u2019s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2","volume":"13","author":"Simon","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ng1096-152","article-title":"Genetic heterogeneity of Bartter\u2019s syndrome revealed by mutations in the K+ channel, ROMK","volume":"14","author":"Simon","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(02)09842-2","article-title":"Association between activating mutations of calcium-sensing receptor and Bartter\u2019s syndrome","volume":"360","author":"Watanabe","year":"2002","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1097\/01.ASN.0000025781.16723.68","article-title":"Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome","volume":"13","author":"Huang","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng0196-24","article-title":"Gitelman\u2019s variant of Bartter\u2019s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter","volume":"12","author":"Simon","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1681\/ASN.2016080881","article-title":"A Novel Hypokalemic-Alkalotic Salt-Losing Tubulopathy in Patients with CLDN10 Mutations","volume":"28","author":"Bongers","year":"2017","journal-title":"JASN"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/gim.2017.71","article-title":"Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome","volume":"20","author":"Brideau","year":"2018","journal-title":"Genet Med"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Klar, J., Piontek, J., Milatz, S., Tariq, M., Jameel, M., Breiderhoff, T., Schuster, J., Fatima, A., Asif, M., and Sher, M. (2017). Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage. PLoS Genet, 13.","DOI":"10.1371\/journal.pgen.1006897"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1053\/j.ajkd.2018.08.015","article-title":"Hypokalemia Associated With a Claudin 10 Mutation: A Case Report","volume":"73","author":"Meyers","year":"2019","journal-title":"Am. J. Kidney Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s00795-009-0482-7","article-title":"Differential expression patterns of the tight junction-associated proteins occludin and claudins in secretory and mature ameloblasts in mouse incisor","volume":"43","author":"Hata","year":"2010","journal-title":"Med. Mol. Morphol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1126\/science.1248571","article-title":"Crystal structure of a claudin provides insight into the architecture of tight junctions","volume":"344","author":"Suzuki","year":"2014","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00424-016-1921-7","article-title":"One gene, two paracellular ion channels-claudin-10 in the kidney","volume":"469","author":"Milatz","year":"2017","journal-title":"Pflugers Arch."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1096\/fj.07-8319com","article-title":"Formation of tight junction: determinants of homophilic interaction between classic claudins","volume":"22","author":"Piontek","year":"2008","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1172\/JCI83942","article-title":"Paracellular epithelial sodium transport maximizes energy efficiency in the kidney","volume":"126","author":"Pei","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1749-6632.2009.04041.x","article-title":"Insights into driving forces and paracellular permeability from claudin-16 knockdown mouse","volume":"1165","author":"Shan","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.kint.2017.08.029","article-title":"Deletion of claudin-10 rescues claudin-16-deficient mice from hypomagnesemia and hypercalciuria","volume":"93","author":"Breiderhoff","year":"2018","journal-title":"Kidney Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jdermsci.2014.08.011","article-title":"Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms","volume":"77","author":"Murota","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/exd.12773","article-title":"Eccrine sweat gland development and sweat secretion","volume":"24","author":"Cui","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00441-010-1089-y","article-title":"Channels and transporters in salivary glands","volume":"343","author":"Roussa","year":"2011","journal-title":"Cell Tissue Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1162348","DOI":"10.1080\/21688370.2016.1162348","article-title":"Current trends in salivary gland tight junctions","volume":"4","author":"Baker","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/prd.12116","article-title":"The physiology of salivary secretion","volume":"70","author":"Proctor","year":"2016","journal-title":"Periodontol. 2000"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0140-6736(00)04140-4","article-title":"Defective cellular trafficking of lacrimal gland aquaporin-5 in Sj\u00f6gren\u2019s syndrome","volume":"357","author":"Tsubota","year":"2001","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"C860","DOI":"10.1152\/ajpcell.00526.2004","article-title":"Fluid secretion and the Na+-K+-2Cl- cotransporter in mouse exorbital lacrimal gland","volume":"289","author":"Walcott","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1542-0124(12)70177-5","article-title":"The aging lacrimal gland: changes in structure and function","volume":"6","author":"Rocha","year":"2008","journal-title":"Ocul Surf"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/exd.13742","article-title":"Maintenance of tight junction barrier integrity in cell turnover and skin diseases","volume":"27","author":"Yokouchi","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1172\/JCI28521","article-title":"Epidermal barrier formation and recovery in skin disorders","volume":"116","author":"Segre","year":"2006","journal-title":"J. Clin. Invest."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1078\/0171-9335-00244","article-title":"Organization and formation of the tight junction system in human epidermis and cultured keratinocytes","volume":"81","author":"Brandner","year":"2002","journal-title":"Eur. J. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/jid.2010.280","article-title":"Resolved psoriasis lesions retain expression of a subset of disease-related genes","volume":"131","author":"Lowes","year":"2011","journal-title":"J. Invest. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.jaci.2012.04.044","article-title":"The broad spectrum of interepithelial junctions in skin and lung","volume":"130","author":"Kast","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.mod.2005.03.001","article-title":"Delayed epidermal permeability barrier formation and hair follicle aberrations in Inv-Cldn6 mice","volume":"122","author":"Troy","year":"2005","journal-title":"Mech. Dev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:30:22Z","timestamp":1760189422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,30]]},"references-count":62,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["ijms20215396"],"URL":"https:\/\/doi.org\/10.3390\/ijms20215396","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,30]]}}}