{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:10:21Z","timestamp":1792789821689,"version":"4.5.0"},"reference-count":85,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Podocyte injury and depletion play a central role in chronic kidney disease (CKD) pathogenesis and progression. However, modeling podocyte loss with temporal control and cell\u2010type specificity remains a major challenge. To address this, we developed a previously undescribed knock\u2010in mouse model, podocyte\u2010specific toxin receptor\u2010mediated cell knockout (Pod\u2010TRECK), expressing the human diphtheria toxin receptor under the endogenous\n                    <jats:italic>Nphs2<\/jats:italic>\n                    (podocin) promoter. This system enables the inducible and podocyte\u2010specific ablation of cells upon diphtheria toxin (DT) administration. We administered graded doses of DT (50\u2013750\u2009ng) and assessed the functional, histological, and molecular consequences of podocyte depletion. We evaluated urinary albumin\u2010to\u2010creatinine ratio, glomerular pathology, and interstitial fibrosis. To characterize transcriptomic changes over time, we performed bulk RNA sequencing on days 5, 14, and 21 post\u2010DT administration. DT treatment induced dose\u2010dependent effects, including albuminuria, nephrin loss, podocyte loss, glomerulosclerosis, and interstitial fibrosis. Transcriptomic profiling revealed a dynamic, time\u2010dependent trajectory. On Day 5, acute inflammatory responses predominated, marked by chemokine and adhesion molecule upregulation. On Day 14, pathways related to cytoskeletal remodeling, extracellular matrix turnover, and mitochondrial dysfunction were enriched. On Day 21, innate immune activity was suppressed, while markers of metabolic exhaustion, oxidative stress, and compensatory antioxidant responses were upregulated. In parallel, we observed a progressive accumulation of oxidative stress\u2010related SNVs (mainly C\u2009&gt;\u2009T and G\u2009&gt;\u2009A), indicating genomic instability driven by sustained oxidative stress. Together, the Pod\u2010TRECK model recapitulates key molecular and pathological features of human CKD progression. This platform provides precise temporal control, enabling robust mechanistic studies and preclinical evaluation of podocyte\u2010targeted therapies.\n                  <\/jats:p>","DOI":"10.1111\/febs.70333","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T03:24:55Z","timestamp":1763004295000},"page":"2291-2313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An inducible and podocyte\u2010specific diphtheria toxin receptor knock\u2010in mouse model for studying glomerular injury and chronic kidney disease progression"],"prefix":"10.1111","volume":"293","author":[{"given":"Masaki","family":"Watanabe","sequence":"first","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine Kitasato University  Towada 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