{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:41:56Z","timestamp":1789774916991,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17be0304321"],"award-info":[{"award-number":["JP17be0304321"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0109451"],"award-info":[{"award-number":["JP20ek0109451"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alport syndrome (AS) is a hereditary disease caused by mutations in the <jats:italic>COL4A5<\/jats:italic> gene and leads to chronic kidney disease. Currently, no specific treatment has been developed. However, a recent study using AS\u2010model mice demonstrated that the exon skipping method could partially rescue the symptoms. In this study, we evaluated the effects of the exon skipping method using kidney organoids generated from AS\u2010patient\u2010derived induced pluripotent stem cells (AS\u2010iPSCs). We generated kidney organoids from AS\u2010iPSCs, which exhibited nephron structures. As expected, the C\u2010terminus of COL4A5 was not expressed in AS\u2010organoids. Interestingly, anti\u2010sense oligonucleotides restored the expression of the C\u2010terminus of COL4A5 in vitro. Next, we transplanted AS\u2010organoids into mice and evaluated glomerular basement membrane formation in vivo. We found that AS\u2010organoids formed a lower slit diaphragm ratio compared to control organoids. Finally, we assessed the effects of exon skipping on transplanted organoids but observed minimum effects. These studies suggest that AS\u2010iPSCs can generate kidney organoids lacking the C\u2010terminus of COL4A5, and that exon skipping can induce its expression in vitro.<\/jats:p>","DOI":"10.1111\/gtc.13170","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T08:46:46Z","timestamp":1729586806000},"page":"1118-1130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Investigation of exon skipping therapy in kidney organoids from Alport syndrome patients derived <scp>iPSCs<\/scp>"],"prefix":"10.1111","volume":"29","author":[{"given":"Kensuke","family":"Yabuuchi","sequence":"first","affiliation":[{"name":"Laboratory for Human Organogenesis RIKEN Center for Biosystems Dynamics Research  Kobe Japan"},{"name":"Department of Development and Regeneration, Graduate School of Medicine Osaka University  Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Horinouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0458-7414","authenticated-orcid":false,"given":"Minoru","family":"Takasato","sequence":"additional","affiliation":[{"name":"Laboratory for Human Organogenesis RIKEN Center for Biosystems Dynamics Research  Kobe Japan"},{"name":"Department of Development and Regeneration, Graduate School of Medicine Osaka University  Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20246326"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1370723"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2009.02.004"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.848389"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.250142"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05203-4"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0325-y"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000090034.71205.74"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.24302"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51235"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-022-00237-4"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16982"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35537-2"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.05.026"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.31662\/jmaj.2021-0019"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73486"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0336-x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03120322"},{"issue":"5","key":"e_1_2_11_20_1","first-page":"1916","article-title":"Portal levels and hepatic clearance of 5\u2010fluorouracil after intraperitoneal administration in humans","volume":"41","author":"Speyer J. L.","year":"1981","journal-title":"Cancer Research"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15695"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.08.003"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13731"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16605-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.04.011"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.131.11.1007"}],"container-title":["Genes to Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gtc.13170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T07:27:33Z","timestamp":1733124453000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gtc.13170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":25,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/gtc.13170"],"URL":"https:\/\/doi.org\/10.1111\/gtc.13170","archive":["Portico"],"relation":{},"ISSN":["1356-9597","1365-2443"],"issn-type":[{"value":"1356-9597","type":"print"},{"value":"1365-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]},"assertion":[{"value":"2024-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}