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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Alport syndrome (AS) is a progressive hereditary nephropathy caused by mutations in COL4A3, COL4A4, or COL4A5, which encode the α3, α4, and α5 chains of type IV collagen. These mutations disrupt the glomerular basement membrane (GBM), leading to hematuria, proteinuria, and eventual renal failure. Although angiotensin II receptor blockers (ARBs) can delay progression, no curative therapies currently exist. Given the monogenic nature of AS, exon skipping therapy offers a promising mutation-specific strategy to restore functional protein expression. This study aimed to evaluate the therapeutic potential of post-onset exon skipping using a tamoxifen-inducible mouse model harboring a patient-derived Col4a5 nonsense mutation.
We generated a novel AS mouse model on a C57BL/6 background carrying a nonsense mutation (R471*) in exon 21 of Col4a5, mimicking a pathogenic variant found in AS patients. To enable temporal and cell-specific control of exon skipping, we further developed a tamoxifen-inducible, podocyte-specific exon 21 skipping model using Cre-loxP technology. Tamoxifen was administered either before or after the onset of proteinuria to assess therapeutic efficacy. Urinary albumin and plasma urea nitrogen (UN) levels, histopathology, and collagen IV α5 expression were evaluated through biochemical assays, histopathology, and transmission electron microscopy.
Tamoxifen-induced exon 21 skipping successfully restored the expression of truncated collagen IV α5 in podocytes. This led to significant improvements in renal injury, including reduced urinary albumin and plasma UN levels. Histopathological analysis revealed amelioration of GBM abnormalities, glomerulosclerosis index, and tubulointerstitial fibrosis. Importantly, treatment initiated after disease onset reversed glomerular damage and improved renal architecture, demonstrating the feasibility of therapeutic intervention even in progressive stages.
Our inducible exon skipping approach in the AS mouse model provides a robust platform for evaluating mutation-targeted therapies. The results support the feasibility and efficacy of exon skipping as a therapeutic strategy for AS, even after disease onset. These findings highlight the potential of post-onset genetic correction in treating monogenic kidney diseases and pave the way for future clinical translation of exon skipping therapies.
