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However, the causal relationship between GBM defects and progressive nephropathy is unknown. We analyzed sequential pathology in a mouse model of XLAS harboring a human nonsense mutation of <jats:italic>COL4A5<\/jats:italic>. In mutant mice, nephropathy commenced from focal GBM irregularity by EM at 6\u00a0weeks of age, prior to exclusive crescents at 13\u00a0weeks of age. Low-vacuum scanning EM demonstrated substantial ragged features in GBM, and crescents were closely associated with fibrinoid exudate, despite lack of GBM break and podocyte depletion at 13\u00a0weeks of age. Crescents were derived from two sites by different cellular components. One was CD44\u2009+\u2009cells, often with fibrinoid exudate in the urinary space, and the other was accumulation of \u03b1-SMA\u2009+\u2009cells in the thickened Bowman\u2019s capsule. These changes finally coalesced, leading to global obliteration. In conclusion, vulnerability of glomerular and capsular barriers to the structural defect in collagen IV may cause non-necrotizing crescents via activation of PECs and migration of interstitial fibroblasts, promoting kidney disease in this model.<\/jats:p>","DOI":"10.1038\/s41598-020-76068-4","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T11:02:41Z","timestamp":1604401361000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bidirectional, non-necrotizing glomerular crescents are the critical pathology in X-linked Alport syndrome mouse model harboring nonsense mutation of human COL4A5"],"prefix":"10.1038","volume":"10","author":[{"given":"Jiang Ying","family":"Song","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Saga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunio","family":"Kawanishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Hashikami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiyasu","family":"Takeyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"76068_CR1","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1136\/bmj.1.3454.504","volume":"1","author":"AC Alport","year":"1927","unstructured":"Alport, A. 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