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Although angiotensin II receptor blockers are available for symptomatic treatment, no radical or curative therapies currently exist. Given the genetic basis of AS, exon-skipping therapy has the potential to serve as a definitive treatment. In this study, we established a tamoxifen-inducible exon 21\u2013skipping mouse model, enabling the evaluation of post-onset therapeutic intervention. We generated a novel AS mouse model harboring a patient-derived nonsense mutation (R471*) in exon 21 of\n                    <jats:italic>Col4a5<\/jats:italic>\n                    on a C57BL\/6 background. Using this strain, we further developed a tamoxifen-inducible, podocyte-specific exon 21\u2013skipping model. Induction of exon skipping, either before or after disease onset, restored truncated collagen IV \u03b15 expression, improved renal function, and ameliorated glomerular and tubular pathology. Notably, treatment initiated after the onset of proteinuria reversed glomerular injury, underscoring its therapeutic potential even in progressive stages. This model provides a robust platform for evaluating mutation-targeted therapies and supports the feasibility of exon-skipping approaches for AS and other monogenic kidney diseases.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-25447-w","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:34:45Z","timestamp":1764081285000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Podocyte specific exon skipping after disease onset improves kidney pathology and function in a mouse model of Alport syndrome"],"prefix":"10.1038","volume":"15","author":[{"given":"Kentarou","family":"Hashikami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryotaro","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Danbayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Nio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"9","key":"25447_CR1","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1681\/ASN.2020071065","volume":"32","author":"J Gibson","year":"2021","unstructured":"Gibson, J. et al. Prevalence estimates of predicted pathogenic COL4A3-col4a5 variants in a population sequencing database and their implications for Alport syndrome. J. Am. Soc. Nephrol. 32(9), 2273\u20132290 (2021).","journal-title":"J. Am. Soc. Nephrol."},{"issue":"11","key":"25447_CR2","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1111\/j.1651-2227.1996.tb13915.x","volume":"85","author":"H Pajari","year":"1996","unstructured":"Pajari, H., K\u00e4\u00e4ri\u00e4inen, H., Muhonen, T. & Koskimies, O. Alport\u2019s syndrome in 78 patients: epidemiological and clinical study. Acta Paediatr. 85(11), 1300\u20131306 (1996).","journal-title":"Acta Paediatr."},{"issue":"2","key":"25447_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.5414\/CNP64085","volume":"64","author":"U Persson","year":"2005","unstructured":"Persson, U., Hertz, J. M., Wieslander, J. & Segelmark, M. Alport syndrome in southern Sweden. Clin. Nephrol. 64(2), 85\u201390 (2005).","journal-title":"Clin. 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