Overlapping Roles of Iroquois Homeobox Genes 3 and 4 in the Compaction of the Ventricular Myocardium
Bibliographic record
Abstract
Left ventricular noncompaction (LVNC) is a primary congenital cardiomyopathy characterized by prominent trabeculation and intra-trabecular recesses in the ventricular wall. Its genetic basis and pathologic mechanism remain largely unknown. Here it is shown that Irx3;Irx4 double knockout (DKO) mouse mutants represent a novel model of LVNC. Irx3 and Irx4 belong to the family of Iroquois homeobox (Irx) genes, encoding transcription factors important for cardiac function. Mice lacking either Irx3 or Irx4 do not have gross cardiac malformations. In contrast, Irx3;Irx4DKO mice exhibit postnatal lethality and thinner ventricular walls as early as E14.5. By P14, DKO mice have prominent noncompacted trabeculation and abnormal muscular growth that resemble human LVNC. Furthermore, Irx3;Irx4DKO hearts exhibit increased expression of heart failure marker genes, elevated Bmp10 pathway activity, and altered pattern of cardiomyocyte proliferation, each of which are implicated in the pathogenesis of LVNC. Taken together, these studies suggest that Irx3 and Irx4 possess overlapping functions, which are essential to myocardial compaction.
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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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".