Revisiting Glomerulopathy in Clusterin Knockout Mice: A Mouse Model of Human Immunotactoid Glomerulopathy
Bibliographic record
Abstract
AIM: Clusterin (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. METHODS: Kidney 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. RESULTS: There 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. CONCLUSION: Our 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".