Bidirectional, non-necrotizing glomerular crescents are the critical pathology in X-linked Alport syndrome mouse model harboring nonsense mutation of human COL4A5.

ABSTRACT: X-linked Alport syndrome (XLAS) is a progressive kidney disease caused by genetic abnormalities of COL4A5. Lack of collagen IV α5 chain staining and "basket-weave" by electron microscopy (EM) in glomerular basement membrane (GBM) are its typical pathology. 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 COL4A5. In mutant mice, nephropathy commenced from focal GBM irregularity by EM at 6 weeks of age, prior to exclusive crescents at 13 weeks 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 weeks of age. Cr

SUBMITTER: Song JY 

PROVIDER: S-EPMC7642296 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature