Shroom3 is required for nephron development (540.9)
Bibliographic record
Abstract
Reduced nephron number is linked with chronic kidney disease and adult onset hypertension. Defects in the formation of nephrons are a major factor in determining nephron number. Multiple genome wide association studies have strongly linked SHROOM3 with altered kidney function and chronic kidney disease. Yet, the role of SHROOM3 in kidney function and nephron formation is not known. We utilized Shroom3‐/‐ and Shroom3+/‐ mutant mice containing a gene trap β‐galactosidase reporter to analyze Shroom3 expression. LacZ expression localized shroom3 to cap mesenchyme and podocytes throughout kidney development. LacZ expression was only observed in the collecting ducts after E15.5. LacZ expression was maintained in the podocyte and collecting ducts in mature kidneys. Immunohistochemistry using a Shroom3 antibody confirmed the dynamic spatial and temporal expression pattern. Histological analysis of kidneys from Shroom3‐/‐ mice demonstrated numerous condensed and cystic glomeruli at E13.5. Abnormal glomeruli demonstrated markedly reduced expression of the podocyte markers Wilms’ Tumor Suppressor‐1 (Wt‐1) and Nephrin in Shroom3‐/‐ mice at E13.5 and E14.5. Glomerular counting at E18.5 demonstrated a 1.6‐fold reduction in glomerular number in Shroom3‐/‐ mice when compared to wild type (n=3). Analysis of postnatal Shroom3 +/‐ mice revealed focal segmental glomerulosclerosis (FSGS), glomerular hypercellularity, and hydronephrosis. Postnatal expression of Wt‐1 was similar to wild‐type mice but nephrin expression was virtually absent. In summary Shroom3 exhibits a dynamic expression pattern and the absence of Shroom3 leads to early defects in nephrogenesis resulting in reduced glomerular number and postnatal glomerular diseases. We conclude that Shroom3 is required for nephron formation or maintenance.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".