Evidence mapPaperPMID 41265459Full record

ArticleNephrology (Carlton, Vic.)2025

Revisiting Glomerulopathy in Clusterin Knockout Mice: A Mouse Model of Human Immunotactoid Glomerulopathy.

Xinglan Li, Xingwei Cai, Qiunong Guan, Junya Tan, Xudan Yang, Changhong Wu, Caigan Du

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Article in Nephrology (Carlton, Vic.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Xinglan LiDepartment of Pathology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Xingwei CaiDepartment of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Qiunong GuanDepartment of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Junya TanLaboratory of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Xudan YangDepartment of Pathology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Changhong WuGuoke Ningbo Life Science and Health Industry Research Institute, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China.
Caigan DuDepartment of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.

Funding

Ningbo Top Medical and Health Research Program 2024020818The Ningbo Major Research and Development Plan Project 2024Z179
6 · The paper itself

Abstract

aimClusterin (CLU) is a chaperone-like glycoprotein, and CLU knockout (KO) mice spontaneously develop age-dependent glomerulopathy with microtubule formation. However, its clinical relevance has not been confirmed yet. Immunotactoid glomerulopathy (ITG) is a clinicopathologic entity of glomerulonephritis characterised by glomerular deposits of electron dense microtubules. This study was to re-examine the glomerulopathy in CLU KO mice as compared with the pathological features of human ITG.

methodsKidney specimens from both wild type C57BL/6 (B6) and CLU-KO B6 mice were analyzed with haematoxylin and eosin, Masson-Trichrome, and Congo-red staining. IgG and DNAJB9 were detected by immunohistochemical staining, and the electron-dense mesangial deposits by transmission electron microscopy. Proteins were identified by liquid chromatography-mass spectrometry.

resultsThere were approximately 75% of glomeruli affected by moderate to severe mesangial lesions in 24-month-old male CLU-KO mice or 85% in 18-month-old female KO mice as compared with little or no glomerular pathology in WT mice at a similar age. The mesangial lesions were stained strongly positive with Masson-Trichrome-stained fibrosis, immunocomplex and anti-IgG, weakly positive with Congo-red, and negative with anti-DNAJB9 antibodies. The electron-dense material in the mesangium was structured with hollow microtubules with an average diameter of 50 nm. Functional enrichments with the STRING database revealed that secreted CLU-bound proteins mainly mediated complement activation and were associated with glomerulonephritis development.

conclusionOur data confirm that the glomerulopathy in CLU-KO B6 mice was similar to the pathological features of ITG and may therefore be considered as an experimental model of ITG. Further, CLU may negatively regulate the fibrillogenesis of ITG.

Indexed as

ClusterinGlomerulonephritisKidney GlomerulusAnimalsDisease Models, AnimalFemaleHumansMaleMice, Inbred C57BLMice, KnockoutMicroscopy, Electron, TransmissionMicrotubulesCLU protein, humanClu protein, mouseClusterinanimal modelclusterin proteinfibrillogenesisimmunotactoid glomerulopathykidney disease

Identifiers

PMID41265459
PMCPMC12634156

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.