The NFATc2 transcription factor is required for normal heart function and signaling in adult mice
Bibliographic record
Abstract
The Ca2+- dependent phosphatase, calcineurin (Cn) and its downstream transcriptional effectors, nuclear factor of activated T-cells (NFAT), are major intracellular modulators of cardiac hypertrophy. In young mice, transcription factor NFATc2 has been identified as the major NFAT isoform responsible for Cn-mediated cardiac hypertrophy. We observed that 7–9 month old NFATc2−/− mice have a higher susceptibility to cardiac dilatation and sudden death, prompting us to monitor changes in heart morphology and growth pathways in this model. Using histology, we show that hearts of adult NFATc2−/− mice display a more dilated left ventricle and thinner interventricular wall. In addition, NFATc2 null hearts have increased GATA-4 expression, higher nuclear transit of GATA-4 and NFATc1, and decreased GSK3-β expression, thus supporting the finding that adult NFATc2−/− mice are more prone to heart failure. Furthermore, angiotensin II-induced cardiac growth reveals that hearts of NFATc2−/− mice hypertrophy to the same extent as wild-type mice, display a thinner myocardial wall and have decreased active AKT and eIF2α expression, suggesting altered translational regulation of myocardial growth. Our collective results propose an uncharacterized role of NFATc2 for normal heart function and growth signaling in adult mice, providing evidence of Cn-signaling being crucial at later stages of life. Supported by CIHR, NSERC and CRC to RNM.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".